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Volumn 72, Issue 7, 2015, Pages 1291-1302

Signaling pathways in mouse and human trophoblast differentiation: A comparative review

Author keywords

Chorionic villi; Cytotrophoblast; Extravillous trophoblast; Labyrinth; Placenta; Syncytiotrophoblast; Trophoblast giant cells; Trophoblast stem cells

Indexed keywords

ACTIVIN; CYCLIC AMP DEPENDENT PROTEIN KINASE; FOCAL ADHESION KINASE; HYPOXIA INDUCIBLE FACTOR; NOTCH RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN NODAL; SCATTER FACTOR; SCATTER FACTOR RECEPTOR; TRANSFORMING GROWTH FACTOR BETA; WNT PROTEIN;

EID: 84938328720     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-014-1794-x     Document Type: Review
Times cited : (114)

References (95)
  • 1
    • 84898601877 scopus 로고    scopus 로고
    • The Human Placenta Project: Placental structure, development, and function in real time
    • 1:STN:280:DC%2BC2crmslCktg%3D%3D 24661567
    • Guttmacher AE, Maddox YT, Spong CY (2014) The Human Placenta Project: placental structure, development, and function in real time. Placenta 35(5):303-304
    • (2014) Placenta , vol.35 , Issue.5 , pp. 303-304
    • Guttmacher, A.E.1    Maddox, Y.T.2    Spong, C.Y.3
  • 3
    • 77950363751 scopus 로고    scopus 로고
    • Development and function of trophoblast giant cells in the rodent placenta
    • 1:CAS:528:DC%2BC3cXltVajtbg%3D 19876834
    • Hu D, Cross JC (2010) Development and function of trophoblast giant cells in the rodent placenta. Int J Dev Biol 54(2-3):341-354
    • (2010) Int J Dev Biol , vol.54 , Issue.2-3 , pp. 341-354
    • Hu, D.1    Cross, J.C.2
  • 5
    • 19744365010 scopus 로고    scopus 로고
    • Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst
    • 1:CAS:528:DC%2BD2MXltFagsbs%3D 15788452
    • Strumpf D, Mao C, Yamanaka Y, Ralston A, Chawengsaksophak K, Beck F, Rossant J (2005) Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst. Development 132(9):2093-2102
    • (2005) Development , vol.132 , Issue.9 , pp. 2093-2102
    • Strumpf, D.1    Mao, C.2    Yamanaka, Y.3    Ralston, A.4    Chawengsaksophak, K.5    Beck, F.6    Rossant, J.7
  • 6
    • 0032509321 scopus 로고    scopus 로고
    • Promotion of trophoblast stem cell proliferation by FGF4
    • 1:CAS:528:DyaK1cXotVOqsrk%3D 9851926
    • Tanaka S, Kunath T, Hadjantonakis AK, Nagy A, Rossant J (1998) Promotion of trophoblast stem cell proliferation by FGF4. Science 282(5396):2072-2075
    • (1998) Science , vol.282 , Issue.5396 , pp. 2072-2075
    • Tanaka, S.1    Kunath, T.2    Hadjantonakis, A.K.3    Nagy, A.4    Rossant, J.5
  • 7
    • 4644245693 scopus 로고    scopus 로고
    • Maintenance of mouse trophoblast stem cell proliferation by TGF-β/activin
    • 1:CAS:528:DC%2BD2cXot1Wku7Y%3D 15464579
    • Erlebacher A, Price KA, Glimcher LH (2004) Maintenance of mouse trophoblast stem cell proliferation by TGF-β/activin. Dev Biol 275(1):158-169
    • (2004) Dev Biol , vol.275 , Issue.1 , pp. 158-169
    • Erlebacher, A.1    Price, K.A.2    Glimcher, L.H.3
  • 9
    • 84873524509 scopus 로고    scopus 로고
    • Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse
    • 1:CAS:528:DC%2BC3sXht1Oksr4%3D 23261930
    • Niakan KK, Eggan K (2013) Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse. Dev Biol 375(1):54-64
    • (2013) Dev Biol , vol.375 , Issue.1 , pp. 54-64
    • Niakan, K.K.1    Eggan, K.2
  • 10
    • 79952145138 scopus 로고    scopus 로고
    • Trophoblast Stem Cells
    • 3043125 1:CAS:528:DC%2BC3MXis1Omtr0%3D 21106963
    • Roberts RM, Fisher SJ (2011) Trophoblast Stem Cells. Biol Reprod 84(3):412-421
    • (2011) Biol Reprod , vol.84 , Issue.3 , pp. 412-421
    • Roberts, R.M.1    Fisher, S.J.2
  • 11
    • 84859160949 scopus 로고    scopus 로고
    • Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation?
    • 1:STN:280:DC%2BC38vks12ksA%3D%3D 22374510
    • James JL, Carter AM, Chamley LW (2012) Human placentation from nidation to 5 weeks of gestation. Part I: what do we know about formative placental development following implantation? Placenta 33(5):327-334
    • (2012) Placenta , vol.33 , Issue.5 , pp. 327-334
    • James, J.L.1    Carter, A.M.2    Chamley, L.W.3
  • 12
    • 77955286814 scopus 로고    scopus 로고
    • ELF5-enforced transcriptional networks define an epigenetically regulated trophoblast stem cell compartment in the human placenta
    • 1:CAS:528:DC%2BC3cXms1Oksbo%3D 20354077
    • Hemberger M, Udayashankar R, Tesar P, Moore H, Burton GJ (2010) ELF5-enforced transcriptional networks define an epigenetically regulated trophoblast stem cell compartment in the human placenta. Hum Mol Genet 19(12):2456-2467
    • (2010) Hum Mol Genet , vol.19 , Issue.12 , pp. 2456-2467
    • Hemberger, M.1    Udayashankar, R.2    Tesar, P.3    Moore, H.4    Burton, G.J.5
  • 13
    • 0030854868 scopus 로고    scopus 로고
    • Activin is a local regulator of human cytotrophoblast cell differentiation
    • 1:CAS:528:DyaK2sXlsFeisb4%3D 9275089
    • Caniggia I, Lye SJ, Cross JC (1997) Activin is a local regulator of human cytotrophoblast cell differentiation. Endocrinology 138(9):3976-3986
    • (1997) Endocrinology , vol.138 , Issue.9 , pp. 3976-3986
    • Caniggia, I.1    Lye, S.J.2    Cross, J.C.3
  • 14
    • 33645085593 scopus 로고    scopus 로고
    • Bi-potential behaviour of cytotrophoblasts in first trimester chorionic villi
    • 1:CAS:528:DC%2BD28XivVakt74%3D 15950280
    • Baczyk D, Dunk C, Huppertz B, Maxwell C, Reister F, Giannoulias D, Kingdom JC (2006) Bi-potential behaviour of cytotrophoblasts in first trimester chorionic villi. Placenta 27(4-5):367-374
    • (2006) Placenta , vol.27 , Issue.4-5 , pp. 367-374
    • Baczyk, D.1    Dunk, C.2    Huppertz, B.3    Maxwell, C.4    Reister, F.5    Giannoulias, D.6    Kingdom, J.C.7
  • 17
    • 0033935126 scopus 로고    scopus 로고
    • The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta
    • 1:CAS:528:DC%2BD3cXkvFKks74%3D 10888880
    • Anson-Cartwright L, Dawson K, Holmyard D, Fisher SJ, Lazzarini RA, Cross JC (2000) The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta. Nat Genet 25(3):311-314
    • (2000) Nat Genet , vol.25 , Issue.3 , pp. 311-314
    • Anson-Cartwright, L.1    Dawson, K.2    Holmyard, D.3    Fisher, S.J.4    Lazzarini, R.A.5    Cross, J.C.6
  • 18
    • 41949088033 scopus 로고    scopus 로고
    • Identification of integrin-alpha4, Rb1, and syncytin a as murine placental target genes of the transcription factor GCMa/Gcm1
    • 1:CAS:528:DC%2BD1cXit1Omtr0%3D 18167345
    • Schubert SW, Lamoureux N, Kilian K, Klein-Hitpass L, Hashemolhosseini S (2008) Identification of integrin-alpha4, Rb1, and syncytin a as murine placental target genes of the transcription factor GCMa/Gcm1. J Biol Chem 283(9):5460-5465
    • (2008) J Biol Chem , vol.283 , Issue.9 , pp. 5460-5465
    • Schubert, S.W.1    Lamoureux, N.2    Kilian, K.3    Klein-Hitpass, L.4    Hashemolhosseini, S.5
  • 19
    • 47649126492 scopus 로고    scopus 로고
    • Early patterning of the chorion leads to the trilaminar trophoblast cell structure in the placental labyrinth
    • 3159581 1:CAS:528:DC%2BD1cXovVGhs7w%3D 18448564
    • Simmons DG, Natale DR, Begay V, Hughes M, Leutz A, Cross JC (2008) Early patterning of the chorion leads to the trilaminar trophoblast cell structure in the placental labyrinth. Development 135(12):2083-2091
    • (2008) Development , vol.135 , Issue.12 , pp. 2083-2091
    • Simmons, D.G.1    Natale, D.R.2    Begay, V.3    Hughes, M.4    Leutz, A.5    Cross, J.C.6
  • 20
    • 2942550705 scopus 로고    scopus 로고
    • The Hand1, Stra13 and Gcm1 transcription factors override FGF signaling to promote terminal differentiation of trophoblast stem cells
    • 1:CAS:528:DC%2BD2cXkvVCksLY%3D 15196947
    • Hughes M, Dobric N, Scott IC, Su L, Starovic M, St-Pierre B, Egan SE, Kingdom JC, Cross JC (2004) The Hand1, Stra13 and Gcm1 transcription factors override FGF signaling to promote terminal differentiation of trophoblast stem cells. Dev Biol 271(1):26-37
    • (2004) Dev Biol , vol.271 , Issue.1 , pp. 26-37
    • Hughes, M.1    Dobric, N.2    Scott, I.C.3    Su, L.4    Starovic, M.5    St-Pierre, B.6    Egan, S.E.7    Kingdom, J.C.8    Cross, J.C.9
  • 21
    • 2542627351 scopus 로고    scopus 로고
    • Complex patterns of GCM1 mRNA and protein in villous and extravillous trophoblast cells of the human placenta
    • 1:CAS:528:DC%2BD2cXjsl2nu7w%3D 15135239
    • Baczyk D, Satkunaratnam A, Nait-Oumesmar B, Huppertz B, Cross JC, Kingdom JC (2004) Complex patterns of GCM1 mRNA and protein in villous and extravillous trophoblast cells of the human placenta. Placenta 25(6):553-559
    • (2004) Placenta , vol.25 , Issue.6 , pp. 553-559
    • Baczyk, D.1    Satkunaratnam, A.2    Nait-Oumesmar, B.3    Huppertz, B.4    Cross, J.C.5    Kingdom, J.C.6
  • 22
    • 67349255287 scopus 로고    scopus 로고
    • Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast
    • 1:CAS:528:DC%2BD1MXks1ygsLs%3D 19219068
    • Baczyk D, Drewlo S, Proctor L, Dunk C, Lye S, Kingdom J (2009) Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast. Cell Death Differ 16(5):719-727
    • (2009) Cell Death Differ , vol.16 , Issue.5 , pp. 719-727
    • Baczyk, D.1    Drewlo, S.2    Proctor, L.3    Dunk, C.4    Lye, S.5    Kingdom, J.6
  • 23
    • 0347928824 scopus 로고    scopus 로고
    • GCMa regulates the syncytin-mediated trophoblastic fusion
    • 1:CAS:528:DC%2BD38XpsFaku7s%3D 12397062
    • Yu C, Shen K, Lin M, Chen P, Lin C, Chang G, Chen H (2002) GCMa regulates the syncytin-mediated trophoblastic fusion. J Biol Chem 277(51):50062-50068
    • (2002) J Biol Chem , vol.277 , Issue.51 , pp. 50062-50068
    • Yu, C.1    Shen, K.2    Lin, M.3    Chen, P.4    Lin, C.5    Chang, G.6    Chen, H.7
  • 24
    • 84881475065 scopus 로고    scopus 로고
    • Ly6e expression is restricted to syncytiotrophoblast cells of the mouse placenta
    • 1:CAS:528:DC%2BC3sXhtVOrsbzJ 23830620
    • Hughes M, Natale BV, Simmons DG, Natale DR (2013) Ly6e expression is restricted to syncytiotrophoblast cells of the mouse placenta. Placenta 34(9):831-835
    • (2013) Placenta , vol.34 , Issue.9 , pp. 831-835
    • Hughes, M.1    Natale, B.V.2    Simmons, D.G.3    Natale, D.R.4
  • 26
    • 0036407347 scopus 로고    scopus 로고
    • Hepatocyte growth factor induced human trophoblast motility involves phosphatidylinositol-3-kinase, mitogen-activated protein kinase, and inducible nitric oxide synthase
    • 1:CAS:528:DC%2BD38XmvFSjsr0%3D 12243747
    • Cartwright JE, Tse WK, Whitley GS (2002) Hepatocyte growth factor induced human trophoblast motility involves phosphatidylinositol-3-kinase, mitogen-activated protein kinase, and inducible nitric oxide synthase. Exp Cell Res 279(2):219-226
    • (2002) Exp Cell Res , vol.279 , Issue.2 , pp. 219-226
    • Cartwright, J.E.1    Tse, W.K.2    Whitley, G.S.3
  • 27
    • 70349786406 scopus 로고    scopus 로고
    • Activin promotes differentiation of cultured mouse trophoblast stem cells towards a labyrinth cell fate
    • 1:CAS:528:DC%2BD1MXht1Onsr%2FK 19716815
    • Natale DRC, Hemberger M, Hughes M, Cross JC (2009) Activin promotes differentiation of cultured mouse trophoblast stem cells towards a labyrinth cell fate. Dev Biol 335(1):120-131
    • (2009) Dev Biol , vol.335 , Issue.1 , pp. 120-131
    • Natale, D.R.C.1    Hemberger, M.2    Hughes, M.3    Cross, J.C.4
  • 28
    • 8144220876 scopus 로고    scopus 로고
    • Nodal protein processing and fibroblast growth factor 4 synergize to maintain a trophoblast stem cell microenvironment
    • 524845 1:CAS:528:DC%2BD2cXhtVWisLvK 15505202
    • Guzman-Ayala M, Ben-Haim N, Beck S, Constam DB (2004) Nodal protein processing and fibroblast growth factor 4 synergize to maintain a trophoblast stem cell microenvironment. PNAS 101(44):15656-15660
    • (2004) PNAS , vol.101 , Issue.44 , pp. 15656-15660
    • Guzman-Ayala, M.1    Ben-Haim, N.2    Beck, S.3    Constam, D.B.4
  • 29
    • 79952003198 scopus 로고    scopus 로고
    • Elsevier Trophoblast Research Award lecture: The multifaceted role of Nodal signaling during mammalian reproduction
    • 21195476
    • Park CB, Dufort D (2011) Elsevier Trophoblast Research Award lecture: the multifaceted role of Nodal signaling during mammalian reproduction. Placenta 32(Suppl 2):S125-S129
    • (2011) Placenta , vol.32 , pp. S125-S129
    • Park, C.B.1    Dufort, D.2
  • 31
    • 0029839156 scopus 로고    scopus 로고
    • Activin-A stimulates, while transforming growth factor beta 1 inhibits, chorionic gonadotrophin production and aromatase activity in cultured human placental trophoblasts
    • 1:CAS:528:DyaK28XntV2lsLw%3D 8916209
    • Song Y, Keelan J, France JT (1996) Activin-A stimulates, while transforming growth factor beta 1 inhibits, chorionic gonadotrophin production and aromatase activity in cultured human placental trophoblasts. Placenta 17(8):603-610
    • (1996) Placenta , vol.17 , Issue.8 , pp. 603-610
    • Song, Y.1    Keelan, J.2    France, J.T.3
  • 33
    • 3843110160 scopus 로고    scopus 로고
    • Nodal and ALK7 inhibit proliferation and induce apoptosis in human trophoblast cells
    • 1:CAS:528:DC%2BD2cXlslOrsrs%3D 15150278
    • Munir S, Xu G, Wu Y, Yang B, Lala PK, Peng C (2004) Nodal and ALK7 inhibit proliferation and induce apoptosis in human trophoblast cells. J Biol Chem 279(30):31277-31286
    • (2004) J Biol Chem , vol.279 , Issue.30 , pp. 31277-31286
    • Munir, S.1    Xu, G.2    Wu, Y.3    Yang, B.4    Lala, P.K.5    Peng, C.6
  • 34
    • 79952751431 scopus 로고    scopus 로고
    • Nodal signals through activin receptor-like kinase 7 to inhibit trophoblast migration and invasion: Implication in the pathogenesis of preeclampsia
    • 3069932 1:CAS:528:DC%2BC3MXktFansbw%3D 21356369
    • Nadeem L, Munir S, Fu G, Dunk C, Baczyk D, Caniggia I, Lye S, Peng C (2011) Nodal signals through activin receptor-like kinase 7 to inhibit trophoblast migration and invasion: implication in the pathogenesis of preeclampsia. Am J Pathol 178(3):1177-1189
    • (2011) Am J Pathol , vol.178 , Issue.3 , pp. 1177-1189
    • Nadeem, L.1    Munir, S.2    Fu, G.3    Dunk, C.4    Baczyk, D.5    Caniggia, I.6    Lye, S.7    Peng, C.8
  • 37
    • 77951251429 scopus 로고    scopus 로고
    • PPARγ regulates trophoblast proliferation and promotes labyrinthine trilineage differentiation
    • 2778869 19956639
    • Parast MM, Yu H, Ciric A, Salata MW, Davis V, Milstone DS (2009) PPARγ regulates trophoblast proliferation and promotes labyrinthine trilineage differentiation. PLoS One 4(11):e8055
    • (2009) PLoS One , vol.4 , Issue.11
    • Parast, M.M.1    Yu, H.2    Ciric, A.3    Salata, M.W.4    Davis, V.5    Milstone, D.S.6
  • 39
    • 0033763069 scopus 로고    scopus 로고
    • Peroxisome proliferator-activated receptor-gamma modulates differentiation of human trophoblast in a ligand-specific manner
    • 1:CAS:528:DC%2BD3cXnsFOgu7Y%3D 11061552
    • Schaiff WT, Carlson MG, Smith SD, Levy R, Nelson DM, Sadovsky Y (2000) Peroxisome proliferator-activated receptor-gamma modulates differentiation of human trophoblast in a ligand-specific manner. J Clin Endocr Metab 85(10):3874-3881
    • (2000) J Clin Endocr Metab , vol.85 , Issue.10 , pp. 3874-3881
    • Schaiff, W.T.1    Carlson, M.G.2    Smith, S.D.3    Levy, R.4    Nelson, D.M.5    Sadovsky, Y.6
  • 40
    • 10044242289 scopus 로고    scopus 로고
    • Troglitazone attenuates hypoxia-induced injury in cultured term human trophoblasts
    • 1:CAS:528:DC%2BD2cXhtVKltrjK 15592306
    • Elchalal U, Humphrey RG, Smith SD, Hu C, Sadovsky Y, Nelson DM (2004) Troglitazone attenuates hypoxia-induced injury in cultured term human trophoblasts. Am J Obstet Gynecol 191(6):2154-2159
    • (2004) Am J Obstet Gynecol , vol.191 , Issue.6 , pp. 2154-2159
    • Elchalal, U.1    Humphrey, R.G.2    Smith, S.D.3    Hu, C.4    Sadovsky, Y.5    Nelson, D.M.6
  • 42
    • 24344502368 scopus 로고    scopus 로고
    • Hypoxia-inducible factor-dependent histone deacetylase activity determines stem cell fate in the placenta
    • 1:CAS:528:DC%2BD2MXpvFOisr0%3D 15987772
    • Maltepe E, Krampitz GW, Okazaki KM, Red-Horse K, Mak W, Simon MC, Fisher SJ (2005) Hypoxia-inducible factor-dependent histone deacetylase activity determines stem cell fate in the placenta. Development 132(15):3393-3403
    • (2005) Development , vol.132 , Issue.15 , pp. 3393-3403
    • Maltepe, E.1    Krampitz, G.W.2    Okazaki, K.M.3    Red-Horse, K.4    Mak, W.5    Simon, M.C.6    Fisher, S.J.7
  • 45
    • 0030768427 scopus 로고    scopus 로고
    • Molecular genetics of implantation in the mouse
    • 1:CAS:528:DyaK2sXmt1Sktbw%3D 9291576
    • Rinkenberger JL, Cross JC, Werb Z (1997) Molecular genetics of implantation in the mouse. Dev Genet 21(1):6-20
    • (1997) Dev Genet , vol.21 , Issue.1 , pp. 6-20
    • Rinkenberger, J.L.1    Cross, J.C.2    Werb, Z.3
  • 48
    • 0023568391 scopus 로고
    • Epidermal growth factor induces differentiation and secretion of human chorionic gonadotropin and placental lactogen in normal human placenta
    • 1:CAS:528:DyaL1cXjt1KrsA%3D%3D 3500181
    • Morrish DW, Bhardwaj D, Dabbagh LK, Marusyk H, Siy O (1987) Epidermal growth factor induces differentiation and secretion of human chorionic gonadotropin and placental lactogen in normal human placenta. J Clin Endocrinol Metab 65(6):1282-1290
    • (1987) J Clin Endocrinol Metab , vol.65 , Issue.6 , pp. 1282-1290
    • Morrish, D.W.1    Bhardwaj, D.2    Dabbagh, L.K.3    Marusyk, H.4    Siy, O.5
  • 49
    • 0027522771 scopus 로고
    • Novel role of human chorionic gonadotropin in differentiation of human cytotrophoblasts
    • 1:CAS:528:DyaK3sXhs1Wgtr4%3D 7679981
    • Shi QJ, Lei ZM, Rao CV, Lin J (1993) Novel role of human chorionic gonadotropin in differentiation of human cytotrophoblasts. Endocrinology 132(3):1387-1395
    • (1993) Endocrinology , vol.132 , Issue.3 , pp. 1387-1395
    • Shi, Q.J.1    Lei, Z.M.2    Rao, C.V.3    Lin, J.4
  • 50
    • 0031956918 scopus 로고    scopus 로고
    • Cyclic AMP-dependent protein kinases and human trophoblast cell differentiation in vitro
    • 1:CAS:528:DyaK1cXivV2htb0%3D 9490643
    • Keryer G, Alsat E, Tasken K, Evain-Brion D (1998) Cyclic AMP-dependent protein kinases and human trophoblast cell differentiation in vitro. J Cell Sci 111(Pt 7):995-1004
    • (1998) J Cell Sci , vol.111 , pp. 995-1004
    • Keryer, G.1    Alsat, E.2    Tasken, K.3    Evain-Brion, D.4
  • 51
    • 0037627414 scopus 로고    scopus 로고
    • Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation
    • 164757 1:CAS:528:DC%2BD3sXjs1yhtrs%3D 12724415
    • Frendo J, Olivier D, Cheynet V, Blond J, Bouton O, Vidaud M, Rabreau M, Evain-Brion D, Mallet F (2003) Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation. Mol Cell Biol 23(10):3566-3574
    • (2003) Mol Cell Biol , vol.23 , Issue.10 , pp. 3566-3574
    • Frendo, J.1    Olivier, D.2    Cheynet, V.3    Blond, J.4    Bouton, O.5    Vidaud, M.6    Rabreau, M.7    Evain-Brion, D.8    Mallet, F.9
  • 52
    • 70350166701 scopus 로고    scopus 로고
    • Placental and embryonic growth restriction in mice with reduced function epidermal growth factor receptor alleles
    • 2746145 1:CAS:528:DC%2BD1MXhtlWksbfM 19564486
    • Dackor J, Caron KM, Threadgill DW (2009) Placental and embryonic growth restriction in mice with reduced function epidermal growth factor receptor alleles. Genetics 183(1):207-218
    • (2009) Genetics , vol.183 , Issue.1 , pp. 207-218
    • Dackor, J.1    Caron, K.M.2    Threadgill, D.W.3
  • 53
    • 84863309182 scopus 로고    scopus 로고
    • A placenta for life
    • 1:CAS:528:DC%2BC38XhtVSgt77K 22578825
    • John R, Hemberger M (2012) A placenta for life. Reprod Biomed Online 25(1):5-11
    • (2012) Reprod Biomed Online , vol.25 , Issue.1 , pp. 5-11
    • John, R.1    Hemberger, M.2
  • 54
    • 34047214754 scopus 로고    scopus 로고
    • Diverse subtypes and developmental origins of trophoblast giant cells in the mouse placenta
    • 1:CAS:528:DC%2BD2sXjvFehtLs%3D 17289015
    • Simmons DG, Fortier AL, Cross JC (2007) Diverse subtypes and developmental origins of trophoblast giant cells in the mouse placenta. Dev Biol 304(2):567-578
    • (2007) Dev Biol , vol.304 , Issue.2 , pp. 567-578
    • Simmons, D.G.1    Fortier, A.L.2    Cross, J.C.3
  • 55
    • 0027350527 scopus 로고
    • Lack of coupling between onset of giant transformation and genome endoreduplication in the mural trophectoderm of the mouse blastocyst
    • 1:STN:280:DyaK3s3htVCqtQ%3D%3D 8459230
    • Gardner RL, Davies TJ (1993) Lack of coupling between onset of giant transformation and genome endoreduplication in the mural trophectoderm of the mouse blastocyst. J Exp Zool 265(1):54-60
    • (1993) J Exp Zool , vol.265 , Issue.1 , pp. 54-60
    • Gardner, R.L.1    Davies, T.J.2
  • 56
    • 0031947965 scopus 로고    scopus 로고
    • Reprogramming the cell cycle for endoreduplication in rodent trophoblast cells
    • 25306 1:CAS:528:DyaK1cXisFSntrY%3D 9529378
    • MacAuley A, Cross JC, Werb Z (1998) Reprogramming the cell cycle for endoreduplication in rodent trophoblast cells. Mol Biol Cell 9(4):795-807
    • (1998) Mol Biol Cell , vol.9 , Issue.4 , pp. 795-807
    • MacAuley, A.1    Cross, J.C.2    Werb, Z.3
  • 57
    • 0035253608 scopus 로고    scopus 로고
    • Trophoblast giant-cell differentiation involves changes in cytoskeleton and cell motility
    • 1:CAS:528:DC%2BD3MXkt1KqtQ%3D%3D 11161561
    • Parast MM, Aeder S, Sutherland AE (2001) Trophoblast giant-cell differentiation involves changes in cytoskeleton and cell motility. Dev Biol 230(1):43-60
    • (2001) Dev Biol , vol.230 , Issue.1 , pp. 43-60
    • Parast, M.M.1    Aeder, S.2    Sutherland, A.E.3
  • 58
    • 84866519031 scopus 로고    scopus 로고
    • Blimp1/Prdm1 governs terminal differentiation of endovascular trophoblast giant cells and defines multipotent progenitors in the developing placenta
    • 3444732 1:CAS:528:DC%2BC38XhsVegu77F 22987638
    • Mould A, Morgan MA, Li L, Bikoff EK, Robertson EJ (2012) Blimp1/Prdm1 governs terminal differentiation of endovascular trophoblast giant cells and defines multipotent progenitors in the developing placenta. Genes Dev 26(18):2063-2074
    • (2012) Genes Dev , vol.26 , Issue.18 , pp. 2063-2074
    • Mould, A.1    Morgan, M.A.2    Li, L.3    Bikoff, E.K.4    Robertson, E.J.5
  • 59
    • 0027615758 scopus 로고
    • Human cytotrophoblast invasion
    • 1:STN:280:DyaK3szltVWqtw%3D%3D 8347835
    • Fisher SJ, Damsky CH (1993) Human cytotrophoblast invasion. Semin Cell Biol 4(3):183-188
    • (1993) Semin Cell Biol , vol.4 , Issue.3 , pp. 183-188
    • Fisher, S.J.1    Damsky, C.H.2
  • 60
    • 0026571678 scopus 로고
    • Distribution patterns of extracellular matrix components and adhesion receptors are intricately modulated during first trimester cytotrophoblast differentiation along the invasive pathway, in vivo
    • 442839 1:CAS:528:DyaK38XotFSgsg%3D%3D 1370295
    • Damsky CH, Fitzgerald ML, Fisher SJ (1992) Distribution patterns of extracellular matrix components and adhesion receptors are intricately modulated during first trimester cytotrophoblast differentiation along the invasive pathway, in vivo. J Clin Invest 89(1):210-222
    • (1992) J Clin Invest , vol.89 , Issue.1 , pp. 210-222
    • Damsky, C.H.1    Fitzgerald, M.L.2    Fisher, S.J.3
  • 61
    • 0030922747 scopus 로고    scopus 로고
    • Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion?
    • 508044 1:CAS:528:DyaK2sXjtFCisbg%3D 9151786
    • Zhou Y, Fisher SJ, Janatpour M, Genbacev O, Dejana E, Wheelock M, Damsky CH (1997) Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion? J Clin Invest 99(9):2139-2151
    • (1997) J Clin Invest , vol.99 , Issue.9 , pp. 2139-2151
    • Zhou, Y.1    Fisher, S.J.2    Janatpour, M.3    Genbacev, O.4    Dejana, E.5    Wheelock, M.6    Damsky, C.H.7
  • 62
    • 34250173484 scopus 로고    scopus 로고
    • A unifying concept of trophoblastic differentiation and malignancy defined by biomarker expression
    • 1:CAS:528:DC%2BD2sXmsFylsL0%3D 17397906
    • Lee Y, Kim K, McKeon F, Yang A, Boyd TK, Crum CP, Parast MM (2007) A unifying concept of trophoblastic differentiation and malignancy defined by biomarker expression. Hum Pathol 38(7):1003-1013
    • (2007) Hum Pathol , vol.38 , Issue.7 , pp. 1003-1013
    • Lee, Y.1    Kim, K.2    McKeon, F.3    Yang, A.4    Boyd, T.K.5    Crum, C.P.6    Parast, M.M.7
  • 63
    • 0033803762 scopus 로고    scopus 로고
    • Localization of E-cadherin in villous, extravillous and vascular trophoblasts during intrauterine, ectopic and molar pregnancy
    • 1:CAS:528:DC%2BD3cXnslSgt7c%3D
    • Floridon C, Nielsen O, Holund B, Sunde L, Westergaard JG, Thomsen SG, Teisner B (2000) Localization of E-cadherin in villous, extravillous and vascular trophoblasts during intrauterine, ectopic and molar pregnancy. Mol Human Reprod 6(10):943-950
    • (2000) Mol Human Reprod , vol.6 , Issue.10 , pp. 943-950
    • Floridon, C.1    Nielsen, O.2    Holund, B.3    Sunde, L.4    Westergaard, J.G.5    Thomsen, S.G.6    Teisner, B.7
  • 65
    • 0022489755 scopus 로고
    • Immunoelectron microscope observations on secretion of human placental lactogen (hPL) in the human chorionic villi
    • 1:CAS:528:DyaL28Xls1Ghur8%3D 3767004
    • Fujimoto S, Hamasaki K, Ueda H, Kagawa H (1986) Immunoelectron microscope observations on secretion of human placental lactogen (hPL) in the human chorionic villi. Anat Rec 216(1):68-72
    • (1986) Anat Rec , vol.216 , Issue.1 , pp. 68-72
    • Fujimoto, S.1    Hamasaki, K.2    Ueda, H.3    Kagawa, H.4
  • 66
    • 82955167925 scopus 로고    scopus 로고
    • hCG, five independent molecules
    • 1:CAS:528:DC%2BC3MXhsFOhtbfJ 22027338
    • Cole LA (2012) hCG, five independent molecules. Clin Chim Acta 413(1-2):48-65
    • (2012) Clin Chim Acta , vol.413 , Issue.1-2 , pp. 48-65
    • Cole, L.A.1
  • 67
    • 34748926103 scopus 로고    scopus 로고
    • Human chorionic gonadotropin produced by the invasive trophoblast but not the villous trophoblast promotes cell invasion and is down-regulated by peroxisome proliferator-activated receptor-gamma
    • 1:CAS:528:DC%2BD2sXhtFWls7bE 17628005
    • Handschuh K, Guibourdenche J, Tsatsaris V, Guesnon M, Laurendeau I, Evain-Brion D, Fournier T (2007) Human chorionic gonadotropin produced by the invasive trophoblast but not the villous trophoblast promotes cell invasion and is down-regulated by peroxisome proliferator-activated receptor-gamma. Endocrinology 148(10):5011-5019
    • (2007) Endocrinology , vol.148 , Issue.10 , pp. 5011-5019
    • Handschuh, K.1    Guibourdenche, J.2    Tsatsaris, V.3    Guesnon, M.4    Laurendeau, I.5    Evain-Brion, D.6    Fournier, T.7
  • 69
    • 77955980851 scopus 로고    scopus 로고
    • Hyperglycosylated hCG, a review
    • 1:CAS:528:DC%2BC3cXpvVGks7o%3D 20619452
    • Cole LA (2010) Hyperglycosylated hCG, a review. Placenta 31(8):653-664
    • (2010) Placenta , vol.31 , Issue.8 , pp. 653-664
    • Cole, L.A.1
  • 71
    • 21444432138 scopus 로고    scopus 로고
    • Tissue-specific and ubiquitous basic helix-loop-helix transcription factors in human placental trophoblasts
    • 1:CAS:528:DC%2BD2MXlvFKlsrg%3D 15993702
    • Meinhardt G, Husslein P, Knöfler M (2005) Tissue-specific and ubiquitous basic helix-loop-helix transcription factors in human placental trophoblasts. Placenta 26(7):527-539
    • (2005) Placenta , vol.26 , Issue.7 , pp. 527-539
    • Meinhardt, G.1    Husslein, P.2    Knöfler, M.3
  • 72
    • 0032509432 scopus 로고    scopus 로고
    • Molecular cloning of the human Hand1 gene/cDNA and its tissue-restricted expression in cytotrophoblastic cells and heart
    • 9931445
    • Knöfler M, Meinhardt G, Vasicek R, Husslein P, Egarter C (1998) Molecular cloning of the human Hand1 gene/cDNA and its tissue-restricted expression in cytotrophoblastic cells and heart. Gene 224(1-2):77-86
    • (1998) Gene , vol.224 , Issue.1-2 , pp. 77-86
    • Knöfler, M.1    Meinhardt, G.2    Vasicek, R.3    Husslein, P.4    Egarter, C.5
  • 73
    • 0036471197 scopus 로고    scopus 로고
    • Human Hand1 basic helix-loop-helix (bHLH) protein: Extra-embryonic expression pattern, interaction partners and identification of its transcriptional repressor domains
    • 1222348 11802795
    • Knöfler M, Meinhardt G, Bauer S, Loregger T, Vasicek R, Bloor DJ, Kimber SJ, Husslein P (2002) Human Hand1 basic helix-loop-helix (bHLH) protein: extra-embryonic expression pattern, interaction partners and identification of its transcriptional repressor domains. Biochem J 361(Pt 3):641-651
    • (2002) Biochem J , vol.361 , pp. 641-651
    • Knöfler, M.1    Meinhardt, G.2    Bauer, S.3    Loregger, T.4    Vasicek, R.5    Bloor, D.J.6    Kimber, S.J.7    Husslein, P.8
  • 74
    • 84875225552 scopus 로고    scopus 로고
    • Homeobox genes and down-stream transcription factor PPARγ in normal and pathological human placental development
    • 1:CAS:528:DC%2BC3sXjtFGltb4%3D 23484914
    • Murthi P, Kalionis B, Cocquebert M, Rajaraman G, Chui A, Keogh RJ, Evain-Brion D, Fournier T (2013) Homeobox genes and down-stream transcription factor PPARγ in normal and pathological human placental development. Placenta 34(4):299-309
    • (2013) Placenta , vol.34 , Issue.4 , pp. 299-309
    • Murthi, P.1    Kalionis, B.2    Cocquebert, M.3    Rajaraman, G.4    Chui, A.5    Keogh, R.J.6    Evain-Brion, D.7    Fournier, T.8
  • 75
    • 0034803507 scopus 로고    scopus 로고
    • Characterization of human villous and extravillous trophoblasts isolated from first trimester placenta
    • 1:CAS:528:DC%2BD3MXnt1Sntrk%3D 11555668
    • Tarrade A, Kuen RL, Malassiné A, Tricottet V, Blain P, Vidaud M, Evain-Brion D (2001) Characterization of human villous and extravillous trophoblasts isolated from first trimester placenta. Lab Invest 81(9):1199-1211
    • (2001) Lab Invest , vol.81 , Issue.9 , pp. 1199-1211
    • Tarrade, A.1    Kuen, R.L.2    Malassiné, A.3    Tricottet, V.4    Blain, P.5    Vidaud, M.6    Evain-Brion, D.7
  • 76
    • 17044399745 scopus 로고    scopus 로고
    • Signalling pathways regulating the invasive differentiation of human trophoblasts: A review
    • 15837062
    • Knöfler M (2005) Signalling pathways regulating the invasive differentiation of human trophoblasts: a review. Placenta 26(Suppl A):S21-S30
    • (2005) Placenta , vol.26 , pp. S21-S30
    • Knöfler, M.1
  • 77
    • 0025895269 scopus 로고
    • Mechanism of control of trophoblast invasion in situ
    • 1:CAS:528:DyaK3MXlvF2lu74%3D 1652588
    • Graham CH, Lala PK (1991) Mechanism of control of trophoblast invasion in situ. J Cell Physiol 148(2):228-234
    • (1991) J Cell Physiol , vol.148 , Issue.2 , pp. 228-234
    • Graham, C.H.1    Lala, P.K.2
  • 78
    • 0026504245 scopus 로고
    • Localization of transforming growth factor-beta at the human fetal-maternal interface: Role in trophoblast growth and differentiation
    • 1:CAS:528:DyaK38XitVymsb0%3D 1374270
    • Graham CH, Lysiak JJ, McCrae KR, Lala PK (1992) Localization of transforming growth factor-beta at the human fetal-maternal interface: role in trophoblast growth and differentiation. Biol Reprod 46(4):561-572
    • (1992) Biol Reprod , vol.46 , Issue.4 , pp. 561-572
    • Graham, C.H.1    Lysiak, J.J.2    McCrae, K.R.3    Lala, P.K.4
  • 79
    • 0030902682 scopus 로고    scopus 로고
    • Effect of transforming growth factor-beta on the plasminogen activator system in cultured first trimester human cytotrophoblasts
    • 1:CAS:528:DyaK2sXislansrg%3D 9089774
    • Graham CH (1997) Effect of transforming growth factor-beta on the plasminogen activator system in cultured first trimester human cytotrophoblasts. Placenta 18(2-3):137-143
    • (1997) Placenta , vol.18 , Issue.2-3 , pp. 137-143
    • Graham, C.H.1
  • 80
    • 84886073116 scopus 로고    scopus 로고
    • Human placental trophoblast invasion and differentiation: A particular focus on Wnt signaling
    • 3783976 24133501
    • Knöfler M, Pollheimer J (2013) Human placental trophoblast invasion and differentiation: a particular focus on Wnt signaling. Front Genet 4:190
    • (2013) Front Genet , vol.4 , pp. 190
    • Knöfler, M.1    Pollheimer, J.2
  • 82
    • 40949155077 scopus 로고    scopus 로고
    • Dickkopf-1 secreted by decidual cells promotes trophoblast cell invasion during murine placentation
    • 1:CAS:528:DC%2BD1cXjvVajur4%3D 18299430
    • Peng S, Li J, Miao C, Jia L, Hu Z, Zhao P, Li J, Zhang Y, Chen Q, Duan E (2008) Dickkopf-1 secreted by decidual cells promotes trophoblast cell invasion during murine placentation. Reproduction 135(3):367-375
    • (2008) Reproduction , vol.135 , Issue.3 , pp. 367-375
    • Peng, S.1    Li, J.2    Miao, C.3    Jia, L.4    Hu, Z.5    Zhao, P.6    Li, J.7    Zhang, Y.8    Chen, Q.9    Duan, E.10
  • 83
    • 84878346492 scopus 로고    scopus 로고
    • Spatiotemporal expression of Notch receptors and ligands in developing mouse placenta
    • 1:CAS:528:DC%2BC3sXpslKrsbk%3D 23665443
    • Gasperowicz M, Rai A, Cross JC (2013) Spatiotemporal expression of Notch receptors and ligands in developing mouse placenta. Gene Expr Patterns 13(7):249-254
    • (2013) Gene Expr Patterns , vol.13 , Issue.7 , pp. 249-254
    • Gasperowicz, M.1    Rai, A.2    Cross, J.C.3
  • 84
    • 79959448545 scopus 로고    scopus 로고
    • A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia
    • 3119307 1:CAS:528:DC%2BC3MXhtVyjsrnL 21693515
    • Hunkapiller NM, Gasperowicz M, Kapidzic M, Plaks V, Maltepe E, Kitajewski J, Cross JC, Fisher SJ (2011) A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia. Development 138(14):2987-2998
    • (2011) Development , vol.138 , Issue.14 , pp. 2987-2998
    • Hunkapiller, N.M.1    Gasperowicz, M.2    Kapidzic, M.3    Plaks, V.4    Maltepe, E.5    Kitajewski, J.6    Cross, J.C.7    Fisher, S.J.8
  • 85
    • 84891472221 scopus 로고    scopus 로고
    • Notch signaling plays a critical role in motility and differentiation of human first-trimester cytotrophoblasts
    • 24189144
    • Haider S, Meinhardt G, Velicky P, Otti GR, Whitley G, Fiala C, Pollheimer J, Knöfler M (2014) Notch signaling plays a critical role in motility and differentiation of human first-trimester cytotrophoblasts. Endocrinology 155(1):263-274
    • (2014) Endocrinology , vol.155 , Issue.1 , pp. 263-274
    • Haider, S.1    Meinhardt, G.2    Velicky, P.3    Otti, G.R.4    Whitley, G.5    Fiala, C.6    Pollheimer, J.7    Knöfler, M.8
  • 86
    • 39149135857 scopus 로고    scopus 로고
    • Maternal hypoxia activates endovascular trophoblast cell invasion
    • 2266816 1:CAS:528:DC%2BD1cXhslKqtLo%3D 18199431
    • Rosario GX, Konno T, Soares MJ (2008) Maternal hypoxia activates endovascular trophoblast cell invasion. Dev Biol 314(2):362-375
    • (2008) Dev Biol , vol.314 , Issue.2 , pp. 362-375
    • Rosario, G.X.1    Konno, T.2    Soares, M.J.3
  • 87
    • 0033637997 scopus 로고    scopus 로고
    • Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure
    • 1885754 1:CAS:528:DC%2BD3MXhsVOjtw%3D%3D 11106583
    • Jauniaux E, Watson AL, Hempstock J, Bao YP, Skepper JN, Burton GJ (2000) Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure. Am J Pathol 157(6):2111-2122
    • (2000) Am J Pathol , vol.157 , Issue.6 , pp. 2111-2122
    • Jauniaux, E.1    Watson, A.L.2    Hempstock, J.3    Bao, Y.P.4    Skepper, J.N.5    Burton, G.J.6
  • 88
    • 0030026954 scopus 로고    scopus 로고
    • Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia
    • 507049 1:CAS:528:DyaK28Xht1Ols78%3D 8567979
    • Genbacev O, Joslin R, Damsky CH, Polliotti BM, Fisher SJ (1996) Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J Clin Invest 97(2):540-550
    • (1996) J Clin Invest , vol.97 , Issue.2 , pp. 540-550
    • Genbacev, O.1    Joslin, R.2    Damsky, C.H.3    Polliotti, B.M.4    Fisher, S.J.5
  • 89
    • 0030879909 scopus 로고    scopus 로고
    • Regulation of human placental development by oxygen tension
    • 1:CAS:528:DyaK2sXmtVSns7c%3D 9287221
    • Genbacev O, Zhou Y, Ludlow JW, Fisher SJ (1997) Regulation of human placental development by oxygen tension. Science 277(5332):1669-1672
    • (1997) Science , vol.277 , Issue.5332 , pp. 1669-1672
    • Genbacev, O.1    Zhou, Y.2    Ludlow, J.W.3    Fisher, S.J.4
  • 90
    • 0034100836 scopus 로고    scopus 로고
    • Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFbeta(3)
    • 289179 1:CAS:528:DC%2BD3cXhslygsb8%3D 10712429
    • Caniggia I, Mostachfi H, Winter J, Gassmann M, Lye SJ, Kuliszewski M, Post M (2000) Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFbeta(3). J Clin Invest 105(5):577-587
    • (2000) J Clin Invest , vol.105 , Issue.5 , pp. 577-587
    • Caniggia, I.1    Mostachfi, H.2    Winter, J.3    Gassmann, M.4    Lye, S.J.5    Kuliszewski, M.6    Post, M.7
  • 91
    • 5044246271 scopus 로고    scopus 로고
    • Both mitogen-activated protein kinase and phosphatidylinositol 3-kinase signalling are required in epidermal growth factor-induced human trophoblast migration
    • 1:CAS:528:DC%2BD2cXntFams7Y%3D 15235105
    • Qiu Q, Yang M, Tsang BK, Gruslin A (2004) Both mitogen-activated protein kinase and phosphatidylinositol 3-kinase signalling are required in epidermal growth factor-induced human trophoblast migration. Mol Hum Reprod 10(9):677-684
    • (2004) Mol Hum Reprod , vol.10 , Issue.9 , pp. 677-684
    • Qiu, Q.1    Yang, M.2    Tsang, B.K.3    Gruslin, A.4
  • 92
    • 77956466583 scopus 로고    scopus 로고
    • Phosphatidylinositol 3 kinase modulation of trophoblast cell differentiation
    • 2944162 20840781
    • Kent LN, Kent LN, Konno T, Soares MJ, Soares MJ (2010) Phosphatidylinositol 3 kinase modulation of trophoblast cell differentiation. BMC Dev Biol 10(1):97
    • (2010) BMC Dev Biol , vol.10 , Issue.1 , pp. 97
    • Kent, L.N.1    Kent, L.N.2    Konno, T.3    Soares, M.J.4    Soares, M.J.5
  • 93
    • 84875522268 scopus 로고    scopus 로고
    • Complete and unidirectional conversion of human embryonic stem cells to trophoblast by BMP4
    • 3612666 1:CAS:528:DC%2BC3sXmsVegurY%3D 23493551
    • Amita M, Adachi K, Alexenko AP, Sinha S, Schust DJ, Schulz LC, Roberts RM, Ezashi T (2013) Complete and unidirectional conversion of human embryonic stem cells to trophoblast by BMP4. PNAS 110(13):E1212-E1221
    • (2013) PNAS , vol.110 , Issue.13 , pp. E1212-E1221
    • Amita, M.1    Adachi, K.2    Alexenko, A.P.3    Sinha, S.4    Schust, D.J.5    Schulz, L.C.6    Roberts, R.M.7    Ezashi, T.8
  • 95
    • 84904154186 scopus 로고    scopus 로고
    • BMP4 regulation of human trophoblast development
    • 25023690
    • Li Y, Parast MM (2014) BMP4 regulation of human trophoblast development. Int J Dev Biol 58(2-4):239-246
    • (2014) Int J Dev Biol , vol.58 , Issue.2-4 , pp. 239-246
    • Li, Y.1    Parast, M.M.2


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