A regulatory network involving β-catenin, e-Cadherin, PI3k/Akt, and slug balances self-renewal and differentiation of human pluripotent stem cells in response to wnt signaling

Stem Cells

Volumn 33, Issue 5, 2015, Pages 1419-1433

  Huang, Tyng Shyan ^a   Li, Li ^a   Moalim Nour, Lilian ^a   Jia, Deyong ^a   Bai, Jian ^a   Yao, Zemin ^a,b   Bennett, Steffany A L ^a,b   Figeys, Daniel ^a,b   Wang, Lisheng ^a,b,c  

^a UNIVERSITY OF OTTAWA   (Canada)

^b SHENYANG PHARMACEUTICAL UNIVERSITY   (China)

^c OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

Author keywords

Differentiation; E cadherin; Human embryonic stem cell; Self renewal; Slug; Wnt; Catenin

Indexed keywords

6 [[2 [[4 (2,4 DICHLOROPHENYL) 5 (4 METHYL 1H IMIDAZOL 2 YL) 2 PYRIMIDINYL]AMINO]ETHYL]AMINO]NICOTINONITRILE; BETA CATENIN; ENHANCED GREEN FLUORESCENT PROTEIN; GLYCOGEN SYNTHASE KINASE 3; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; T CELL FACTOR PROTEIN; TRANSCRIPTION FACTOR SLUG; TRANSCRIPTION FACTOR SNAIL; UVOMORULIN; WNT3A PROTEIN; CADHERIN; PROTEIN KINASE INHIBITOR; SNAIL FAMILY TRANSCRIPTION FACTORS; TRANSCRIPTION FACTOR;

ARTICLE; CELL DIFFERENTIATION; CELL JUNCTION; CELL MEMBRANE; CELL RENEWAL; CELLULAR DISTRIBUTION; CONTROLLED STUDY; CYTOPLASM; EMBRYONIC STEM CELL; ENZYME ACTIVATION; ENZYME INHIBITION; HUMAN; HUMAN CELL; PLURIPOTENT STEM CELL; PROTEIN EXPRESSION; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; UPREGULATION; WNT SIGNALING PATHWAY; ANTAGONISTS AND INHIBITORS; CELL SELF-RENEWAL; CYTOLOGY; DOWN REGULATION; DRUG EFFECTS; GENE REGULATORY NETWORK; METABOLISM;

BETA CATENIN; CADHERINS; CELL DIFFERENTIATION; CELL SELF RENEWAL; DOWN-REGULATION; ENZYME ACTIVATION; GENE REGULATORY NETWORKS; GLYCOGEN SYNTHASE KINASE 3; HUMANS; PHOSPHATIDYLINOSITOL 3-KINASES; PLURIPOTENT STEM CELLS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; TCF TRANSCRIPTION FACTORS; TRANSCRIPTION FACTORS; UP-REGULATION; WNT SIGNALING PATHWAY;

EID: 84928543691     PISSN: 10665099     EISSN: 15494918     Source Type: Journal    
DOI: 10.1002/stem.1944     Document Type: Article

References (66)

1. ten Berge D, Kurek D, Blauwkamp T, et al. Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells. Nat Cell Biol 2011; 13: 1070-1075.
2. Sato N, Meijer L, Skaltsounis L, et al. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 2004; 10: 55-63.
3. Singla DK, Schneider DJ, LeWinter MM, et al. wnt3a but not wnt11 supports self-renewal of embryonic stem cells. Biochem Biophys Res Commun 2006; 345: 789-795.
4. Miki T, Yasuda SY, Kahn M,. Wnt/beta-catenin signaling in embryonic stem cell self-renewal and somatic cell reprogramming. Stem Cell Rev 2011; 7: 836-846.
5. Doble BW, Patel S, Wood GA, et al. Functional redundancy of GSK-3alpha and GSK-3beta in Wnt/beta-catenin signaling shown by using an allelic series of embryonic stem cell lines. Dev Cell 2007; 12: 957-971.
6. Hanna J, Markoulaki S, Mitalipova M, et al. Metastable pluripotent states in NOD-mouse-derived ESCs. Cell Stem Cell 2009; 4: 513-524.
7. Ying QL, Wray J, Nichols J, et al. The ground state of embryonic stem cell self-renewal. Nature 2008; 453: 519-523.
8. Fernandez A, Huggins IJ, Perna L, et al. The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells. Proc Natl Acad Sci USA 2014; 111: 1409-1414.
9. Lluis F, Pedone E, Pepe S, et al. Periodic activation of Wnt/beta-catenin signaling enhances somatic cell reprogramming mediated by cell fusion. Cell Stem Cell 2008; 3: 493-507.
10. Marson A, Foreman R, Chevalier B, et al. Wnt signaling promotes reprogramming of somatic cells to pluripotency. Cell Stem Cell 2008; 3: 132-135.
11. Bakre MM, Hoi A, Mong JC, et al. Generation of multipotential mesendodermal progenitors from mouse embryonic stem cells via sustained Wnt pathway activation. J Biol Chem 2007; 282: 31703-31712.
12. Dravid G, Ye Z, Hammond H, et al. Defining the role of Wnt/beta-catenin signaling in the survival, proliferation, and self-renewal of human embryonic stem cells. Stem Cells 2005; 23: 1489-1501.
13. Davidson KC, Adams AM, Goodson JM, et al. Wnt/beta-catenin signaling promotes differentiation, not self-renewal, of human embryonic stem cells and is repressed by Oct4. Proc Natl Acad Sci USA 2012; 109: 4485-4490.
14. Singh AM, Reynolds D, Cliff T, et al. Signaling network crosstalk in human pluripotent cells: A Smad2/3-regulated switch that controls the balance between self-renewal and differentiation. Cell Stem Cell 2012; 10: 312-326.
15. Anton R, Kestler HA, Kuhl M,. Beta-catenin signaling contributes to stemness and regulates early differentiation in murine embryonic stem cells. FEBS Lett 2007; 581: 5247-5254.
16. Wagner RT, Xu X, Yi F, et al. Canonical Wnt/beta-catenin regulation of liver receptor homolog-1 mediates pluripotency gene expression. Stem Cells 2010; 28: 1794-1804.
17. Clevers H, Nusse R,. Wnt/beta-catenin signaling and disease. Cell 2012; 149: 1192-1205.
18. Nelson WJ, Nusse R,. Convergence of Wnt, beta-catenin, and cadherin pathways. Science 2004; 303: 1483-1487.
19. Angers S, Moon RT,. Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol 2009; 10: 468-477.
20. Cole MF, Johnstone SE, Newman JJ, et al. Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells. Genes Dev 2008; 22: 746-755.
21. Saegusa M, Hashimura M, Kuwata T, et al. Requirement of the Akt/beta-catenin pathway for uterine carcinosarcoma genesis, modulating E-cadherin expression through the transactivation of slug. Am J Pathol 2009; 174: 2107-2115.
22. McCrea PD, Turck CW, Gumbiner B,. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science 1991; 254: 1359-1361.
23. Carpenter MK, Frey-Vasconcells J, Rao MS,. Developing safe therapies from human pluripotent stem cells. Nat Biotechnol 2009; 27: 606-613.
24. Larue L, Antos C, Butz S, et al. A role for cadherins in tissue formation. Development 1996; 122: 3185-3194.
25. Chou YF, Chen HH, Eijpe M, et al. The growth factor environment defines distinct pluripotent ground states in novel blastocyst-derived stem cells. Cell 2008; 135: 449-461.
26. Xu Y, Zhu X, Hahm HS, et al. Revealing a core signaling regulatory mechanism for pluripotent stem cell survival and self-renewal by small molecules. Proc Natl Acad Sci USA 2010; 107: 8129-8134.
27. Li L, Wang S, Jezierski A, et al. A unique interplay between Rap1 and E-cadherin in the endocytic pathway regulates self-renewal of human embryonic stem cells. Stem Cells 2010; 28: 247-257.
28. Li L, Wang BH, Wang S, et al. Individual cell movement, asymmetric colony expansion, Rho-associated kinase and E-cadherin impact the clonogenicity of human embryonic stem cells. Biophys J 2010; 98: 2442-2451.
29. Ohgushi M, Matsumura M, Eiraku M, et al. Molecular pathway and cell state responsible for dissociation-induced apoptosis in human pluripotent stem cells. Cell Stem Cell 2010; 7: 225-239.
30. Chen G, Hou Z, Gulbranson DR, et al. Actin-myosin contractility is responsible for the reduced viability of dissociated human embryonic stem cells. Cell Stem Cell 2010; 7: 240-248.
31. Chen T, Yuan D, Wei B, et al. E-cadherin-mediated cell-cell contact is critical for induced pluripotent stem cell generation. Stem Cells 2010; 28: 1315-1325.
32. Redmer T, Diecke S, Grigoryan T, et al. E-cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming. EMBO Rep 2011; 12: 720-726.
33. Samavarchi-Tehrani P, Golipour A, David L, et al. Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. Cell Stem Cell 2010; 7: 64-77.
34. Li R, Liang J, Ni S, et al. A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell 2010; 7: 51-63.
35. Gafni O, Weinberger L, Mansour AA, et al. Derivation of novel human ground state naive pluripotent stem cells. Nature 2013; 504: 282-286.
36. Watanabe K, Dai X,. A WNTer revisit: New faces of beta-catenin and TCFs in pluripotency. Sci Signal 2011; 4: pe41.
37. Wang S, Tian R, Li L, et al. An enhanced chemically defined SILAC culture system for quantitative proteomics study of human embryonic stem cells. Proteomics 2011; 11: 4040-4046.
38. Jo H, Mondal S, Tan D, et al. Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death. Proc Natl Acad Sci USA 2012; 109: 10581-10586.
39. Gottardi CJ, Wong E, Gumbiner BM,. E-cadherin suppresses cellular transformation by inhibiting beta-catenin signaling in an adhesion-independent manner. J Cell Biol 2001; 153: 1049-1060.
40. Stappert J, Kemler R,. A short core region of E-cadherin is essential for catenin binding and is highly phosphorylated. Cell Adhes Commun 1994; 2: 319-327.
41. Kolligs FT, Hu G, Dang CV, et al. Neoplastic transformation of RK3E by mutant beta-catenin requires deregulation of Tcf/Lef transcription but not activation of c-myc expression. Mol Cell Biol 1999; 19: 5696-5706.
42. Gupta PB, Kuperwasser C, Brunet JP, et al. The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. Nat Genet 2005; 37: 1047-1054.
43. Sarbassov DD, Guertin DA, Ali SM, et al. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307: 1098-1101.
44. Fuerer C, Nusse R,. Lentiviral vectors to probe and manipulate the Wnt signaling pathway. PLoS One 2010; 5: e9370.
45. Jia D, Yang W, Li L, et al. β-Catenin and NF-κB co-activation triggered by TLR3 stimulation facilitates stem cell-like phenotypes in breast cancer. Cell Death Differ. 2014 Sep 26. doi: 10.1038/cdd.2014.145. [Epub ahead of print]
46. Tsutsui H, Valamehr B, Hindoyan A, et al. An optimized small molecule inhibitor cocktail supports long-term maintenance of human embryonic stem cells. Nat Commun 2011; 2: 167.
47. Wray J, Kalkan T, Gomez-Lopez S, et al. Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation. Nat Cell Biol 2011; 13: 838-845.
48. Kemler R, Hierholzer A, Kanzler B, et al. Stabilization of beta-catenin in the mouse zygote leads to premature epithelial-mesenchymal transition in the epiblast. Development 2004; 131: 5817-5824.
49. McLean AB, D'Amour KA, Jones KL, et al. Activin a efficiently specifies definitive endoderm from human embryonic stem cells only when phosphatidylinositol 3-kinase signaling is suppressed. Stem Cells 2007; 25: 29-38.
50. Nusse R,. Wnt signaling and stem cell control. Cell Res 2008; 18: 523-527.
51. Staal FJ, Noort Mv M, Strous GJ, et al. Wnt signals are transmitted through N-terminally dephosphorylated beta-catenin. EMBO Rep 2002; 3: 63-68.
52. van Noort M, Meeldijk J, van der Zee R, et al. Wnt signaling controls the phosphorylation status of beta-catenin. J Biol Chem 2002; 277: 17901-17905.
53. Sakai D, Tanaka Y, Endo Y, et al. Regulation of Slug transcription in embryonic ectoderm by beta-catenin-Lef/Tcf and BMP-Smad signaling. Dev Growth Differ 2005; 47: 471-482.
54. Lyashenko N, Winter M, Migliorini D, et al. Differential requirement for the dual functions of beta-catenin in embryonic stem cell self-renewal and germ layer formation. Nat Cell Biol 2011; 13: 753-761.
55. Kelly KF, Ng DY, Jayakumaran G, et al. beta-catenin enhances Oct-4 activity and reinforces pluripotency through a TCF-independent mechanism. Cell Stem Cell 2011; 8: 214-227.
56. Blauwkamp TA, Nigam S, Ardehali R, et al. Endogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors. Nat Commun 2012; 3: 1070.
57. Kim H, Wu J, Ye S, et al. Modulation of beta-catenin function maintains mouse epiblast stem cell and human embryonic stem cell self-renewal. Nat Commun 2013; 4: 2403.
58. Storm MP, Bone HK, Beck CG, et al. Regulation of Nanog expression by phosphoinositide 3-kinase-dependent signaling in murine embryonic stem cells. J Biol Chem 2007; 282: 6265-6273.
59. Watanabe K, Ueno M, Kamiya D, et al. A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nat Biotechnol 2007; 25: 681-686.
60. Faunes F, Hayward P, Descalzo SM, et al. A membrane-associated beta-catenin/Oct4 complex correlates with ground-state pluripotency in mouse embryonic stem cells. Development 2013; 140: 1171-1183.
61. Livigni A, Peradziryi H, Sharov AA, et al. A conserved Oct4/POUV-dependent network links adhesion and migration to progenitor maintenance. Curr Biol 2013; 23: 2233-2244.
62. Torres VA, Tapia JC, Rodriguez DA, et al. E-cadherin is required for caveolin-1-mediated down-regulation of the inhibitor of apoptosis protein survivin via reduced beta-catenin-Tcf/Lef-dependent transcription. Mol Cell Biol 2007; 27: 7703-7717.
63. Maher MT, Flozak AS, Stocker AM, et al. Activity of the beta-catenin phosphodestruction complex at cell-cell contacts is enhanced by cadherin-based adhesion. J Cell Biol 2009; 186: 219-228.
64. Fernando RI, Litzinger M, Trono P, et al. The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells. J Clin Invest 2010; 120: 533-544.
65. Pera MF, Tam PP,. Extrinsic regulation of pluripotent stem cells. Nature 2010; 465: 713-720.
66. Laprise P, Langlois MJ, Boucher MJ, et al. Down-regulation of MEK/ERK signaling by E-cadherin-dependent PI3K/Akt pathway in differentiating intestinal epithelial cells. J Cell Physiol 2004; 199: 32-39.