Deciphering Hematopoietic Stem Cells in Their Niches: A Critical Appraisal of Genetic Models, Lineage Tracing, and Imaging Strategies

Cell Stem Cell

Volumn 13, Issue 5, 2013, Pages 520-533

  Joseph, Chacko ^a,b   Quach, Julie M ^a   Walkley, Carl R ^a,b   Lane, Steven W ^c   Lo Celso, Cristina ^d   Purton, Louise E ^a,b  

^a ST VINCENT'S INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c UNIVERSITY OF QUEENSLAND   (Australia)

^d IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

THYMIDINE KINASE;

CELL FUNCTION; CELL INTERACTION; CELL ISOLATION; CELL LINEAGE; CONFOCAL LASER SCANNING MICROSCOPY; GENETIC MODEL; GENETICALLY ENGINEERED MOUSE STRAIN; HEMATOPOIETIC STEM CELL; IMAGING; INTRAVITAL MICROSCOPY; LASER SCANNING CYTOMETRY; NONHUMAN; PRIORITY JOURNAL; REVIEW; STEM CELL NICHE; ANIMAL; BIOLOGICAL MODEL; CYTOLOGY; DIAGNOSTIC IMAGING; HUMAN; PHYSIOLOGY;

ANIMALS; CELL LINEAGE; DIAGNOSTIC IMAGING; HEMATOPOIETIC STEM CELLS; HUMANS; MODELS, BIOLOGICAL; MODELS, GENETIC; STEM CELL NICHE;

EID: 84902292966     PISSN: 19345909     EISSN: 18759777     Source Type: Journal    
DOI: 10.1016/j.stem.2013.10.010     Document Type: Review

References (146)

1. Alva, J.A., Zovein, A.C., Monvoisin, A., Murphy, T., Salazar, A., Harvey, N.L., Carmeliet, P., Iruela-Arispe, M.L., VE-Cadherin-Cre-recombinase transgenic mouse: a tool for lineage analysis and gene deletion in endothelial cells. Dev. Dyn. 235 (2006), 759–767.
2. Arai, F., Hirao, A., Ohmura, M., Sato, H., Matsuoka, S., Takubo, K., Ito, K., Koh, G.Y., Suda, T., Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118 (2004), 149–161.
3. Asada, N., Katayama, Y., Sato, M., Minagawa, K., Wakahashi, K., Kawano, H., Kawano, Y., Sada, A., Ikeda, K., Matsui, T., Tanimoto, M., Matrix-embedded osteocytes regulate mobilization of hematopoietic stem/progenitor cells. Cell Stem Cell 12 (2013), 737–747.
4. Askmyr, M., Sims, N.A., Martin, T.J., Purton, L.E., What is the true nature of the osteoblastic hematopoietic stem cell niche?. Trends Endocrinol. Metab. 20 (2009), 303–309.
5. Balordi, F., Fishell, G., Mosaic removal of hedgehog signaling in the adult SVZ reveals that the residual wild-type stem cells have a limited capacity for self-renewal. J. Neurosci. 27 (2007), 14248–14259.
6. Bivi, N., Condon, K.W., Allen, M.R., Farlow, N., Passeri, G., Brun, L.R., Rhee, Y., Bellido, T., Plotkin, L.I., Cell autonomous requirement of connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation. J. Bone Miner. Res. 27 (2012), 374–389.
7. Blanpain, C., Tracing the cellular origin of cancer. Nat. Cell Biol. 15 (2013), 126–134.
8. Blanpain, C., Simons, B.D., Unravelling stem cell dynamics by lineage tracing. Nat. Rev. Mol. Cell Biol. 14 (2013), 489–502.
9. Bradford, G.B., Williams, B., Rossi, R., Bertoncello, I., Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment. Exp. Hematol. 25 (1997), 445–453.
10. Brockschnieder, D., Lappe-Siefke, C., Goebbels, S., Boesl, M.R., Nave, K.A., Riethmacher, D., Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination. Mol. Cell. Biol. 24 (2004), 7636–7642.
11. Bromberg, O., Frisch, B.J., Weber, J.M., Porter, R.L., Civitelli, R., Calvi, L.M., Osteoblastic N-cadherin is not required for microenvironmental support and regulation of hematopoietic stem and progenitor cells. Blood 120 (2012), 303–313.
12. Cha, J.H., Chang, M.Y., Richardson, J.A., Eidels, L., Transgenic mice expressing the diphtheria toxin receptor are sensitive to the toxin. Mol. Microbiol. 49 (2003), 235–240.
13. Chen, J., Kwon, C.H., Lin, L., Li, Y., Parada, L.F., Inducible site-specific recombination in neural stem/progenitor cells. Genesis 47 (2009), 122–131.
14. Clatch, R.J., Foreman, J.R., Five-color immunophenotyping plus DNA content analysis by laser scanning cytometry. Cytometry 34 (1998), 36–38.
15. Clatch, R.J., Walloch, J.L., Zutter, M.M., Kamentsky, L.A., Immunophenotypic analysis of hematologic malignancy by laser scanning cytometry. Am. J. Clin. Pathol. 105 (1996), 744–755.
16. Clatch, R.J., Foreman, J.R., Walloch, J.L., Simplified immunophenotypic analysis by laser scanning cytometry. Cytometry 34 (1998), 3–16.
17. Cochrane, R.L., Clark, S.H., Harris, A., Kream, B.E., Rearrangement of a conditional allele regardless of inheritance of a Cre recombinase transgene. Genesis 45 (2007), 17–20.
18. Constien, R., Forde, A., Liliensiek, B., Gröne, H.J., Nawroth, P., Hämmerling, G., Arnold, B., Characterization of a novel EGFP reporter mouse to monitor Cre recombination as demonstrated by a Tie2 Cre mouse line. Genesis 30 (2001), 36–44.
19. Croker, B.A., Metcalf, D., Robb, L., Wei, W., Mifsud, S., DiRago, L., Cluse, L.A., Sutherland, K.D., Hartley, L., Williams, E., et al. SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis. Immunity 20 (2004), 153–165.
20. Dacic, S., Kalajzic, I., Visnjic, D., Lichtler, A.C., Rowe, D.W., Col1a1-driven transgenic markers of osteoblast lineage progression. J. Bone Miner. Res. 16 (2001), 1228–1236.
21. Dacquin, R., Starbuck, M., Schinke, T., Karsenty, G., Mouse alpha1(I)-collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast. Dev. Dyn. 224 (2002), 245–251.
22. Davey, R.A., Clarke, M.V., Sastra, S., Skinner, J.P., Chiang, C., Anderson, P.H., Zajac, J.D., Decreased body weight in young Osterix-Cre transgenic mice results in delayed cortical bone expansion and accrual. Transgenic Res. 21 (2012), 885–893.
23. de Boer, J., Williams, A., Skavdis, G., Harker, N., Coles, M., Tolaini, M., Norton, T., Williams, K., Roderick, K., Potocnik, A.J., Kioussis, D., Transgenic mice with hematopoietic and lymphoid specific expression of Cre. Eur. J. Immunol. 33 (2003), 314–325.
24. de Lange, W.J., Halabi, C.M., Beyer, A.M., Sigmund, C.D., Germ line activation of the Tie2 and SMMHC promoters causes noncell-specific deletion of floxed alleles. Physiol. Genomics 35 (2008), 1–4.
25. Dexter, T.M., Allen, T.D., Lajtha, L.G., Schofield, R., Lord, B.I., Stimulation of differentiation and proliferation of haemopoietic cells in vitro. J. Cell. Physiol. 82 (1973), 461–473.
26. Dexter, T.M., Allen, T.D., Lajtha, L.G., Conditions controlling the proliferation of haemopoietic stem cells in vitro. J. Cell. Physiol. 91 (1977), 335–344.
27. Ding, L., Morrison, S.J., Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature 495 (2013), 231–235.
28. Ding, L., Saunders, T.L., Enikolopov, G., Morrison, S.J., Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481 (2012), 457–462.
29. Dominici, M., Rasini, V., Bussolari, R., Chen, X., Hofmann, T.J., Spano, C., Bernabei, D., Veronesi, E., Bertoni, F., Paolucci, P., et al. Restoration and reversible expansion of the osteoblastic hematopoietic stem cell niche after marrow radioablation. Blood 114 (2009), 2333–2343.
30. Dubois, N.C., Hofmann, D., Kaloulis, K., Bishop, J.M., Trumpp, A., Nestin-Cre transgenic mouse line Nes-Cre1 mediates highly efficient Cre/loxP mediated recombination in the nervous system, kidney, and somite-derived tissues. Genesis 44 (2006), 355–360.
31. Dworkin, S., Malaterre, J., Hollande, F., Darcy, P.K., Ramsay, R.G., Mantamadiotis, T., cAMP response element binding protein is required for mouse neural progenitor cell survival and expansion. Stem Cells 27 (2009), 1347–1357.
32. Elefteriou, F., Yang, X., Genetic mouse models for bone studies—strengths and limitations. Bone 49 (2011), 1242–1254.
33. Essers, M.A., Offner, S., Blanco-Bose, W.E., Waibler, Z., Kalinke, U., Duchosal, M.A., Trumpp, A., IFNalpha activates dormant haematopoietic stem cells in vivo. Nature 458 (2009), 904–908.
34. Feil, R., Brocard, J., Mascrez, B., LeMeur, M., Metzger, D., Chambon, P., Ligand-activated site-specific recombination in mice. Proc. Natl. Acad. Sci. USA 93 (1996), 10887–10890.
35. Feng, J.Q., Huang, H., Lu, Y., Ye, L., Xie, Y., Tsutsui, T.W., Kunieda, T., Castranio, T., Scott, G., Bonewald, L.B., Mishina, Y., The Dentin matrix protein 1 (Dmp1) is specifically expressed in mineralized, but not soft, tissues during development. J. Dent. Res. 82 (2003), 776–780.
36. Fuchs, E., Horsley, V., Ferreting out stem cells from their niches. Nat. Cell Biol. 13 (2011), 513–518.
37. Fulzele, K., Krause, D.S., Panaroni, C., Saini, V., Barry, K.J., Liu, X., Lotinun, S., Baron, R., Bonewald, L., Feng, J.Q., et al. Myelopoiesis is regulated by osteocytes through Gsα-dependent signaling. Blood 121 (2013), 930–939.
38. Georgiades, P., Ogilvy, S., Duval, H., Licence, D.R., Charnock-Jones, D.S., Smith, S.K., Print, C.G., VavCre transgenic mice: a tool for mutagenesis in hematopoietic and endothelial lineages. Genesis 34 (2002), 251–256.
39. Gerstner, A.O., Trumpfheller, C., Racz, P., Osmancik, P., Tenner-Racz, K., Tárnok, A., Quantitative histology by multicolor slide-based cytometry. Cytometry A 59 (2004), 210–219.
40. Gonzalez-Nieto, D., Li, L., Kohler, A., Ghiaur, G., Ishikawa, E., Sengupta, A., Madhu, M., Arnett, J.L., Santho, R.A., Dunn, S.K., et al. Connexin-43 in the osteogenic BM niche regulates its cellular composition and the bidirectional traffic of hematopoietic stem cells and progenitors. Blood 119 (2012), 5144–5154.
41. Göthert, J.R., Gustin, S.E., van Eekelen, J.A., Schmidt, U., Hall, M.A., Jane, S.M., Green, A.R., Göttgens, B., Izon, D.J., Begley, C.G., Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium. Blood 104 (2004), 1769–1777.
42. Göthert, J.R., Gustin, S.E., Hall, M.A., Green, A.R., Göttgens, B., Izon, D.J., Begley, C.G., In vivo fate-tracing studies using the Scl stem cell enhancer: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis. Blood 105 (2005), 2724–2732.
43. Göttgens, B., Nastos, A., Kinston, S., Piltz, S., Delabesse, E.C., Stanley, M., Sanchez, M.J., Ciau-Uitz, A., Patient, R., Green, A.R., Establishing the transcriptional programme for blood: the SCL stem cell enhancer is regulated by a multiprotein complex containing Ets and GATA factors. EMBO J. 21 (2002), 3039–3050.
44. Göttgens, B., Broccardo, C., Sanchez, M.J., Deveaux, S., Murphy, G., Göthert, J.R., Kotsopoulou, E., Kinston, S., Delaney, L., Piltz, S., et al. The scl +18/19 stem cell enhancer is not required for hematopoiesis: identification of a 5′ bifunctional hematopoietic-endothelial enhancer bound by Fli-1 and Elf-1. Mol. Cell. Biol. 24 (2004), 1870–1883.
45. Grant, M.B., May, W.S., Caballero, S., Brown, G.A., Guthrie, S.M., Mames, R.N., Byrne, B.J., Vaught, T., Spoerri, P.E., Peck, A.B., Scott, E.W., Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat. Med. 8 (2002), 607–612.
46. Greenbaum, A., Hsu, Y.M., Day, R.B., Schuettpelz, L.G., Christopher, M.J., Borgerding, J.N., Nagasawa, T., Link, D.C., CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature 495 (2013), 227–230.
47. Hall, M.A., Curtis, D.J., Metcalf, D., Elefanty, A.G., Sourris, K., Robb, L., Gothert, J.R., Jane, S.M., Begley, C.G., The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12. Proc. Natl. Acad. Sci. USA 100 (2003), 992–997.
48. Hameyer, D., Loonstra, A., Eshkind, L., Schmitt, S., Antunes, C., Groen, A., Bindels, E., Jonkers, J., Krimpenfort, P., Meuwissen, R., et al. Toxicity of ligand-dependent Cre recombinases and generation of a conditional Cre deleter mouse allowing mosaic recombination in peripheral tissues. Physiol. Genomics 31 (2007), 32–41.
49. Harnett, M.M., Laser scanning cytometry: understanding the immune system in situ. Nat. Rev. Immunol. 7 (2007), 897–904.
50. Hartner, J.C., Walkley, C.R., Lu, J., Orkin, S.H., ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nat. Immunol. 10 (2009), 109–115.
51. Henriksen, M., Miller, B., Newmark, J., Al-Kofahi, Y., Holden, E., Laser scanning cytometry and its applications: a pioneering technology in the field of quantitative imaging cytometry. Methods Cell Biol. 102 (2011), 161–205.
52. Heyman, R.A., Borrelli, E., Lesley, J., Anderson, D., Richman, D.D., Baird, S.M., Hyman, R., Evans, R.M., Thymidine kinase obliteration: creation of transgenic mice with controlled immune deficiency. Proc. Natl. Acad. Sci. USA 86 (1989), 2698–2702.
53. Hirschi, K.K., Hemogenic endothelium during development and beyond. Blood 119 (2012), 4823–4827.
54. Hooper, A.T., Butler, J.M., Nolan, D.J., Kranz, A., Iida, K., Kobayashi, M., Kopp, H.G., Shido, K., Petit, I., Yanger, K., et al. Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells. Cell Stem Cell 4 (2009), 263–274.
55. Isakoff, M.S., Sansam, C.G., Tamayo, P., Subramanian, A., Evans, J.A., Fillmore, C.M., Wang, X., Biegel, J.A., Pomeroy, S.L., Mesirov, J.P., Roberts, C.W., Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation. Proc. Natl. Acad. Sci. USA 102 (2005), 17745–17750.
56. Kalajzic, I., Braut, A., Guo, D., Jiang, X., Kronenberg, M.S., Mina, M., Harris, M.A., Harris, S.E., Rowe, D.W., Dentin matrix protein 1 expression during osteoblastic differentiation, generation of an osteocyte GFP-transgene. Bone 35 (2004), 74–82.
57. Kiel, M.J., Yilmaz, O.H., Iwashita, T., Yilmaz, O.H., Terhorst, C., Morrison, S.J., SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121 (2005), 1109–1121.
58. Kiel, M.J., He, S., Ashkenazi, R., Gentry, S.N., Teta, M., Kushner, J.A., Jackson, T.L., Morrison, S.J., Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature 449 (2007), 238–242.
59. Kisanuki, Y.Y., Hammer, R.E., Miyazaki, J., Williams, S.C., Richardson, J.A., Yanagisawa, M., Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo. Dev. Biol. 230 (2001), 230–242.
60. Köhler, A., Schmithorst, V., Filippi, M.D., Ryan, M.A., Daria, D., Gunzer, M., Geiger, H., Altered cellular dynamics and endosteal location of aged early hematopoietic progenitor cells revealed by time-lapse intravital imaging in long bones. Blood 114 (2009), 290–298.
61. Koni, P.A., Joshi, S.K., Temann, U.A., Olson, D., Burkly, L., Flavell, R.A., Conditional vascular cell adhesion molecule 1 deletion in mice: impaired lymphocyte migration to bone marrow. J. Exp. Med. 193 (2001), 741–754.
62. Krause, D.S., Scadden, D.T., Preffer, F.I., The hematopoietic stem cell niche—home for friend and foe?. Cytometry B Clin. Cytom. 84 (2013), 7–20.
63. Kühn, R., Schwenk, F., Aguet, M., Rajewsky, K., Inducible gene targeting in mice. Science 269 (1995), 1427–1429.
64. Kunisaki, Y., Bruns, I., Scheiermann, C., Ahmed, J., Pinho, S., Zhang, D., Mizoguchi, T., Wei, Q., Lucas, D., Ito, K., et al. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature, 2013, 10.1038/nature12612 in press. Published online October 9, 2013.
65. Lazer, G., Katzav, S., Guanine nucleotide exchange factors for RhoGTPases: good therapeutic targets for cancer therapy?. Cell. Signal. 23 (2011), 969–979.
66. Lendahl, U., Zimmerman, L.B., McKay, R.D., CNS stem cells express a new class of intermediate filament protein. Cell 60 (1990), 585–595.
67. Lengner, C.J., Steinman, H.A., Gagnon, J., Smith, T.W., Henderson, J.E., Kream, B.E., Stein, G.S., Lian, J.B., Jones, S.N., Osteoblast differentiation and skeletal development are regulated by Mdm2-p53 signaling. J. Cell Biol. 172 (2006), 909–921.
68. Lewandowski, D., Barroca, V., Ducongé F., Bayer, J., Van Nhieu, J.T., Pestourie, C., Fouchet, P., Tavitian, B., Roméo, P.H., In vivo cellular imaging pinpoints the role of reactive oxygen species in the early steps of adult hematopoietic reconstitution. Blood 115 (2010), 443–452.
69. Liu, F., Woitge, H.W., Braut, A., Kronenberg, M.S., Lichtler, A.C., Mina, M., Kream, B.E., Expression and activity of osteoblast-targeted Cre recombinase transgenes in murine skeletal tissues. Int. J. Dev. Biol. 48 (2004), 645–653.
70. Livet, J., Weissman, T.A., Kang, H., Draft, R.W., Lu, J., Bennis, R.A., Sanes, J.R., Lichtman, J.W., Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 450 (2007), 56–62.
71. Lo Celso, C., Fleming, H.E., Wu, J.W., Zhao, C.X., Miake-Lye, S., Fujisaki, J., Côté D., Rowe, D.W., Lin, C.P., Scadden, D.T., Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature 457 (2009), 92–96.
72. Lo Celso, C., Lin, C.P., Scadden, D.T., In vivo imaging of transplanted hematopoietic stem and progenitor cells in mouse calvarium bone marrow. Nat. Protoc. 6 (2011), 1–14.
73. Logan, M., Martin, J.F., Nagy, A., Lobe, C., Olson, E.N., Tabin, C.J., Expression of Cre Recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis 33 (2002), 77–80.
74. Lu, Y., Xie, Y., Zhang, S., Dusevich, V., Bonewald, L.F., Feng, J.Q., DMP1-targeted Cre expression in odontoblasts and osteocytes. J. Dent. Res. 86 (2007), 320–325.
75. Madisen, L., Zwingman, T.A., Sunkin, S.M., Oh, S.W., Zariwala, H.A., Gu, H., Ng, L.L., Palmiter, R.D., Hawrylycz, M.J., Jones, A.R., et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13 (2010), 133–140.
76. Maes, C., Kobayashi, T., Kronenberg, H.M., A novel transgenic mouse model to study the osteoblast lineage in vivo. Ann. N Y Acad. Sci. 1116 (2007), 149–164.
77. Maes, C., Kobayashi, T., Selig, M.K., Torrekens, S., Roth, S.I., Mackem, S., Carmeliet, G., Kronenberg, H.M., Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev. Cell 19 (2010), 329–344.
78. Maisonpierre, P.C., Suri, C., Jones, P.F., Bartunkova, S., Wiegand, S.J., Radziejewski, C., Compton, D., McClain, J., Aldrich, T.H., Papadopoulos, N., et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277 (1997), 55–60.
79. Mao, X., Fujiwara, Y., Orkin, S.H., Improved reporter strain for monitoring Cre recombinase-mediated DNA excisions in mice. Proc. Natl. Acad. Sci. USA 96 (1999), 5037–5042.
80. Martin, J.F., Bradley, A., Olson, E.N., The paired-like homeo box gene MHox is required for early events of skeletogenesis in multiple lineages. Genes Dev. 9 (1995), 1237–1249.
81. Martins, R.A., Zindy, F., Donovan, S., Zhang, J., Pounds, S., Wey, A., Knoepfler, P.S., Eisenman, R.N., Roussel, M.F., Dyer, M.A., N-myc coordinates retinal growth with eye size during mouse development. Genes Dev. 22 (2008), 179–193.
82. Mazo, I.B., Gutierrez-Ramos, J.C., Frenette, P.S., Hynes, R.O., Wagner, D.D., von Andrian, U.H., Hematopoietic progenitor cell rolling in bone marrow microvessels: parallel contributions by endothelial selectins and vascular cell adhesion molecule 1. J. Exp. Med. 188 (1998), 465–474.
83. Méndez-Ferrer, S., Michurina, T.V., Ferraro, F., Mazloom, A.R., Macarthur, B.D., Lira, S.A., Scadden, D.T., Ma'ayan, A., Enikolopov, G.N., Frenette, P.S., Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466 (2010), 829–834.
84. Migliaccio, A.R., Carta, C., Migliaccio, G., In vivo expansion of purified hematopoietic stem cells transplanted in nonablated W/Wv mice. Exp. Hematol. 27 (1999), 1655–1666.
85. Mignone, J.L., Kukekov, V., Chiang, A.S., Steindler, D., Enikolopov, G., Neural stem and progenitor cells in nestin-GFP transgenic mice. J. Comp. Neurol. 469 (2004), 311–324.
86. Monvoisin, A., Alva, J.A., Hofmann, J.J., Zovein, A.C., Lane, T.F., Iruela-Arispe, M.L., VE-cadherin-CreERT2 transgenic mouse: a model for inducible recombination in the endothelium. Dev. Dyn. 235 (2006), 3413–3422.
87. Motoike, T., Loughna, S., Perens, E., Roman, B.L., Liao, W., Chau, T.C., Richardson, C.D., Kawate, T., Kuno, J., Weinstein, B.M., et al. Universal GFP reporter for the study of vascular development. Genesis 28 (2000), 75–81.
88. Muzumdar, M.D., Tasic, B., Miyamichi, K., Li, L., Luo, L., A global double-fluorescent Cre reporter mouse. Genesis 45 (2007), 593–605.
89. Nakamura-Ishizu, A., Suda, T., Hematopoietic stem cell niche: an interplay among a repertoire of multiple functional niches. Biochim. Biophys. Acta 1830 (2013), 2404–2409.
90. Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J.M., Behringer, R.R., de Crombrugghe, B., The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108 (2002), 17–29.
91. Nombela-Arrieta, C., Pivarnik, G., Winkel, B., Canty, K.J., Harley, B., Mahoney, J.E., Park, S.Y., Lu, J., Protopopov, A., Silberstein, L.E., Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment. Nat. Cell Biol. 15 (2013), 533–543.
92. Ogilvy, S., Metcalf, D., Gibson, L., Bath, M.L., Harris, A.W., Adams, J.M., Promoter elements of vav drive transgene expression in vivo throughout the hematopoietic compartment. Blood 94 (1999), 1855–1863.
93. Ohishi, M., Ono, W., Ono, N., Khatri, R., Marzia, M., Baker, E.K., Root, S.H., Wilson, T.L., Iwamoto, Y., Kronenberg, H.M., et al. A novel population of cells expressing both hematopoietic and mesenchymal markers is present in the normal adult bone marrow and is augmented in a murine model of marrow fibrosis. Am. J. Pathol. 180 (2012), 811–818.
94. Oswald, J., Jørgensen, B., Pompe, T., Kobe, F., Salchert, K., Bornhäuser, M., Ehninger, G., Werner, C., Comparison of flow cytometry and laser scanning cytometry for the analysis of CD34+ hematopoietic stem cells. Cytometry A 57 (2004), 100–107.
95. Park, D., Spencer, J.A., Koh, B.I., Kobayashi, T., Fujisaki, J., Clemens, T.L., Lin, C.P., Kronenberg, H.M., Scadden, D.T., Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. Cell Stem Cell 10 (2012), 259–272.
96. Pinho, S., Lacombe, J., Hanoun, M., Mizoguchi, T., Bruns, I., Kunisaki, Y., Frenette, P.S., PDGFRα and CD51 mark human nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion. J. Exp. Med. 210 (2013), 1351–1367.
97. Plum, L., Rother, E., Münzberg, H., Wunderlich, F.T., Morgan, D.A., Hampel, B., Shanabrough, M., Janoschek, R., Könner, A.C., Alber, J., et al. Enhanced leptin-stimulated Pi3k activation in the CNS promotes white adipose tissue transdifferentiation. Cell Metab. 6 (2007), 431–445.
98. Poulos, M.G., Guo, P., Kofler, N.M., Pinho, S., Gutkin, M.C., Tikhonova, A., Aifantis, I., Frenette, P.S., Kitajewski, J., Rafii, S., Butler, J.M., Endothelial jagged-1 is necessary for homeostatic and regenerative hematopoiesis. Cell Rep 4 (2013), 1022–1034.
99. Progatzky, F., Dallman, M.J., Lo Celso, C., From seeing to believing: labelling strategies for in vivo cell-tracking experiments. Interface Focus, 3, 2013, 20130001.
100. Rankin, E.B., Wu, C., Khatri, R., Wilson, T.L., Andersen, R., Araldi, E., Rankin, A.L., Yuan, J., Kuo, C.J., Schipani, E., Giaccia, A.J., The HIF signaling pathway in osteoblasts directly modulates erythropoiesis through the production of EPO. Cell 149 (2012), 63–74.
101. Robb, L., Lyons, I., Li, R., Hartley, L., Köntgen, F., Harvey, R.P., Metcalf, D., Begley, C.G., Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl gene. Proc. Natl. Acad. Sci. USA 92 (1995), 7075–7079.
102. Rodda, S.J., McMahon, A.P., Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 133 (2006), 3231–3244.
103. Saito, M., Iwawaki, T., Taya, C., Yonekawa, H., Noda, M., Inui, Y., Mekada, E., Kimata, Y., Tsuru, A., Kohno, K., Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice. Nat. Biotechnol. 19 (2001), 746–750.
104. Scheller, E.L., Song, J., Dishowitz, M.I., Soki, F.N., Hankenson, K.D., Krebsbach, P.H., Leptin functions peripherally to regulate differentiation of mesenchymal progenitor cells. Stem Cells 28 (2010), 1071–1080.
105. Schlaeger, T.M., Bartunkova, S., Lawitts, J.A., Teichmann, G., Risau, W., Deutsch, U., Sato, T.N., Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice. Proc. Natl. Acad. Sci. USA 94 (1997), 3058–3063.
106. Schnürch, H., Risau, W., Expression of tie-2, a member of a novel family of receptor tyrosine kinases, in the endothelial cell lineage. Development 119 (1993), 957–968.
107. Schofield, R., The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4 (1978), 7–25.
108. Scott, M.M., Lachey, J.L., Sternson, S.M., Lee, C.E., Elias, C.F., Friedman, J.M., Elmquist, J.K., Leptin targets in the mouse brain. J. Comp. Neurol. 514 (2009), 518–532.
109. Shimshek, D.R., Kim, J., Hübner, M.R., Spergel, D.J., Buchholz, F., Casanova, E., Stewart, A.F., Seeburg, P.H., Sprengel, R., Codon-improved Cre recombinase (iCre) expression in the mouse. Genesis 32 (2002), 19–26.
110. Sipkins, D.A., Wei, X., Wu, J.W., Runnels, J.M., Côté D., Means, T.K., Luster, A.D., Scadden, D.T., Lin, C.P., In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature 435 (2005), 969–973.
111. Snippert, H.J., van der Flier, L.G., Sato, T., van Es, J.H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A.M., van Rheenen, J., Simons, B.D., Clevers, H., Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 143 (2010), 134–144.
112. Sörensen, I., Adams, R.H., Gossler, A., DLL1-mediated Notch activation regulates endothelial identity in mouse fetal arteries. Blood 113 (2009), 5680–5688.
113. Soriano, P., Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat. Genet. 21 (1999), 70–71.
114. Soriano, P., Friedrich, G., Lawinger, P., Promoter interactions in retrovirus vectors introduced into fibroblasts and embryonic stem cells. J. Virol. 65 (1991), 2314–2319.
115. Srinivas, S., Watanabe, T., Lin, C.S., William, C.M., Tanabe, Y., Jessell, T.M., Costantini, F., Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev. Biol., 1, 2001, 4.
116. Sugiyama, T., Kohara, H., Noda, M., Nagasawa, T., Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25 (2006), 977–988.
117. Sun, J.F., Phung, T., Shiojima, I., Felske, T., Upalakalin, J.N., Feng, D., Kornaga, T., Dor, T., Dvorak, A.M., Walsh, K., Benjamin, L.E., Microvascular patterning is controlled by fine-tuning the Akt signal. Proc. Natl. Acad. Sci. USA 102 (2005), 128–133.
118. Takaku, T., Malide, D., Chen, J., Calado, R.T., Kajigaya, S., Young, N.S., Hematopoiesis in 3 dimensions: human and murine bone marrow architecture visualized by confocal microscopy. Blood 116 (2010), e41–e55.
119. Takakura, N., Huang, X.L., Naruse, T., Hamaguchi, I., Dumont, D.J., Yancopoulos, G.D., Suda, T., Critical role of the TIE2 endothelial cell receptor in the development of definitive hematopoiesis. Immunity 9 (1998), 677–686.
120. Tang, Y., Harrington, A., Yang, X., Friesel, R.E., Liaw, L., The contribution of the Tie2+ lineage to primitive and definitive hematopoietic cells. Genesis 48 (2010), 563–567.
121. Tárnok, A., Gerstner, A.O., Clinical applications of laser scanning cytometry. Cytometry 50 (2002), 133–143.
122. Theis, M., de Wit, C., Schlaeger, T.M., Eckardt, D., Krüger, O., Döring, B., Risau, W., Deutsch, U., Pohl, U., Willecke, K., Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene. Genesis 29 (2001), 1–13.
123. Trentin, J.J., Determination of bone marrow stem cell differentiation by stromal hemopoietic inductive microenvironments (HIM). Am. J. Pathol. 65 (1971), 621–628.
124. Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P.C., Bock, R., Klein, R., Schütz, G., Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat. Genet. 23 (1999), 99–103.
125. Trumpp, A., Depew, M.J., Rubenstein, J.L., Bishop, J.M., Martin, G.R., Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. Genes Dev. 13 (1999), 3136–3148.
126. Tumbar, T., Guasch, G., Greco, V., Blanpain, C., Lowry, W.E., Rendl, M., Fuchs, E., Defining the epithelial stem cell niche in skin. Science 303 (2004), 359–363.
127. Turan, S., Galla, M., Ernst, E., Qiao, J., Voelkel, C., Schiedlmeier, B., Zehe, C., Bode, J., Recombinase-mediated cassette exchange (RMCE): traditional concepts and current challenges. J. Mol. Biol. 407 (2011), 193–221.
128. Visnjic, D., Kalajzic, I., Gronowicz, G., Aguila, H.L., Clark, S.H., Lichtler, A.C., Rowe, D.W., Conditional ablation of the osteoblast lineage in Col2.3deltatk transgenic mice. J. Bone Miner. Res. 16 (2001), 2222–2231.
129. Visnjic, D., Kalajzic, Z., Rowe, D.W., Katavic, V., Lorenzo, J., Aguila, H.L., Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood 103 (2004), 3258–3264.
130. Visvader, J.E., Fujiwara, Y., Orkin, S.H., Unsuspected role for the T-cell leukemia protein SCL/tal-1 in vascular development. Genes Dev. 12 (1998), 473–479.
131. Walkley, C.R., Qudsi, R., Sankaran, V.G., Perry, J.A., Gostissa, M., Roth, S.I., Rodda, S.J., Snay, E., Dunning, P., Fahey, F.H., et al. Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev. 22 (2008), 1662–1676.
132. Wang, L., Benedito, R., Bixel, M.G., Zeuschner, D., Stehling, M., Sävendahl, L., Haigh, J.J., Snippert, H., Clevers, H., Breier, G., et al. Identification of a clonally expanding haematopoietic compartment in bone marrow. EMBO J. 32 (2013), 219–230.
133. Wiese, C., Rolletschek, A., Kania, G., Blyszczuk, P., Tarasov, K.V., Tarasova, Y., Wersto, R.P., Boheler, K.R., Wobus, A.M., Nestin expression—a property of multi-lineage progenitor cells?. Cell. Mol. Life Sci. 61 (2004), 2510–2522.
134. Wilson, A., Laurenti, E., Oser, G., van der Wath, R.C., Blanco-Bose, W., Jaworski, M., Offner, S., Dunant, C.F., Eshkind, L., Bockamp, E., et al. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell 135 (2008), 1118–1129.
135. Wojcik, E.M., Saraga, S.A., Jin, J.K., Hendricks, J.B., Application of laser scanning cytometry for evaluation of DNA ploidy in routine cytologic specimens. Diagn. Cytopathol. 24 (2001), 200–205.
136. Wolf, N.S., Trentin, J.J., Hemopoietic colony studies. V. Effect of hemopoietic organ stroma on differentiation of pluripotent stem cells. J. Exp. Med. 127 (1968), 205–214.
137. Wu, J.Y., Purton, L.E., Rodda, S.J., Chen, M., Weinstein, L.S., McMahon, A.P., Scadden, D.T., Kronenberg, H.M., Osteoblastic regulation of B lymphopoiesis is mediated by Gsalpha-dependent signaling pathways. Proc. Natl. Acad. Sci. USA 105 (2008), 16976–16981.
138. Xiao, Z., Dallas, M., Qiu, N., Nicolella, D., Cao, L., Johnson, M., Bonewald, L., Quarles, L.D., Conditional deletion of Pkd1 in osteocytes disrupts skeletal mechanosensing in mice. FASEB J. 25 (2011), 2418–2432.
139. Xie, Y., Yin, T., Wiegraebe, W., He, X.C., Miller, D., Stark, D., Perko, K., Alexander, R., Schwartz, J., Grindley, J.C., et al. Detection of functional haematopoietic stem cell niche using real-time imaging. Nature 457 (2009), 97–101.
140. Xiong, J., Onal, M., Jilka, R.L., Weinstein, R.S., Manolagas, S.C., O'Brien, C.A., Matrix-embedded cells control osteoclast formation. Nat. Med. 17 (2011), 1235–1241.
141. Zabaglo, L., Ormerod, M.G., Dowsett, M., Measurement of proliferation marker Ki67 in breast tumour FNAs using laser scanning cytometry in comparison to conventional immunocytochemistry. Cytometry B Clin. Cytom. 56 (2003), 55–61.
142. Zambrowicz, B.P., Imamoto, A., Fiering, S., Herzenberg, L.A., Kerr, W.G., Soriano, P., Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc. Natl. Acad. Sci. USA 94 (1997), 3789–3794.
143. Zhao, C., Blum, J., Chen, A., Kwon, H.Y., Jung, S.H., Cook, J.M., Lagoo, A., Reya, T., Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo. Cancer Cell 12 (2007), 528–541.
144. Zhao, H., Halicka, H.D., Traganos, F., Jorgensen, E., Darzynkiewicz, Z., New biomarkers probing depth of cell senescence assessed by laser scanning cytometry. Cytometry A 77 (2010), 999–1007.
145. Zimmerman, L., Parr, B., Lendahl, U., Cunningham, M., McKay, R., Gavin, B., Mann, J., Vassileva, G., McMahon, A., Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron 12 (1994), 11–24.
146. Zovein, A.C., Hofmann, J.J., Lynch, M., French, W.J., Turlo, K.A., Yang, Y., Becker, M.S., Zanetta, L., Dejana, E., Gasson, J.C., et al. Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell 3 (2008), 625–636.