The role of hypoxia in stem cell potency and differentiation

Regenerative Medicine

Volumn 8, Issue 6, 2013, Pages 771-782

  Hawkins, Kate E ^a   Sharp, Tyson V ^b   Mckay, Tristan R ^a,b  

^a ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

differentiation; HSC; hypoxia; iPS; MSC; niche; pluripotency; self renewal; stem cell; stem cell O2

Indexed keywords

CELL DNA; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; OXYGEN; VASCULOTROPIN;

AEROBIC METABOLISM; CELL DIFFERENTIATION; CELL EXPANSION; CELL GROWTH; CELL HYPOXIA; CELL ISOLATION; CELL RENEWAL; CELL TRANSFORMATION; CELL VIABILITY; DNA DAMAGE; DNA MODIFICATION; EMBRYO DEVELOPMENT; EMBRYONIC STEM CELL; EXTRACELLULAR MATRIX; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HIF 1ALPHA GENE; HIF 2ALPHA GENE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MESENCHYMAL STEM CELL TRANSPLANTATION; MITOCHONDRIAL RESPIRATION; NEURAL STEM CELL; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REGENERATIVE MEDICINE; REVIEW; STEM CELL MOBILIZATION; STEM CELL NICHE; STEM CELL TRANSPLANTATION; THERAPY EFFECT; TISSUE REGENERATION; VEGF GENE;

ADULT STEM CELLS; ANIMALS; CELL DIFFERENTIATION; CELL HYPOXIA; HUMANS; PLURIPOTENT STEM CELLS; STEM CELLS;

EID: 84886455520     PISSN: 17460751     EISSN: 1746076X     Source Type: Journal    
DOI: 10.2217/rme.13.71     Document Type: Review

References (130)

1. Levy AP, Levy NS, Wegner S, Goldberg MA. Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J. Biol. Chem. 270(22), 13333-13340 (1995
2. Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol. Cell. Biol. 12(12), 5447-5454 (1992
3. Forristal CE, Wright KL, Hanley NA, Oreffo RO, Houghton FD. Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions. Reproduction 139(1), 85-97 (2010
4. Yu F, White SB, Zhao Q, Lee FS. HIF 1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc. Natl Acad. Sci. USA 98(17), 9630-9635 (2001
5. Jaakkola P, Mole DR, Tian YM et al. Targeting of HIF alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292(5516), 468-472 (2001
6. Ivan M, Kondo K, Yang H et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science 292(5516), 464-468 (2001
7. Maxwell PH, Wiesener MS, Chang GW et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-Dependent proteolysis. Nature 399(6733), 271-275 (1999
8. Foxler DE, Bridge KS, James V et al. The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF 1 activity. Nat. Cell. Biol. 14(2), 201-208 (2012
9. Bertout JA, Patel SA, Simon MC. The impact of O2 availability on human cancer. Nat. Rev. Cancer 8(12), 967-975 (2008
10. Raval RR, Lau KW, Tran MG et al. Contrasting properties of hypoxia-inducible factor 1 (HIF 1) and HIF 2 in von Hippel-Lindau-Associated renal cell carcinoma. Mol. Cell. Biol. 25(13), 5675-5686 (2005
11. Heikkila M, Pasanen A, Kivirikko KI, Myllyharju J. Roles of the human hypoxia-inducible factor (HIF)-3alpha variants in the hypoxia response. Cell. Mol. Life Sci. 68(23), 3885-3901 (2011
12. Csete M. Oxygen in the cultivation of stem cells. Ann. N.Y. Acad. Sci. 1049, 1-8 (2005
13. Romero-Moya D, Bueno C, Montes R et al. Cord blood-Derived CD34+ hematopoietic cells with low mitochondrial mass are enriched in hematopoietic repopulating stem cell function. Haematologica 98(7), 1022-1029 (2013
14. Ottosen LD, Hindkaer J, Husth M, Petersen DE, Kirk J, Ingerslev HJ. Observations on intrauterine oxygen tension measured by fibre-optic microsensors. Reprod. Biomed. Online 13(3), 380-385 (2006
15. Iyer NV, Kotch LE, Agani F et al. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev. 12(2), 149-162 (1998
16. Ryan HE, Lo J, Johnson RS. HIF 1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J. 17(11), 3005-3015 (1998
17. Tian H, Hammer RE, Matsumoto AM, Russell DW, McKnight SL. The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev. 12(21), 3320-3324 (1998
18. Peng J, Zhang L, Drysdale L, Fong GH. The transcription factor EPAS-1/hypoxia-inducible factor 2alpha plays an important role in vascular remodeling. Proc. Natl Acad. Sci. USA 97(15), 8386-8391 (2000
19. Kozak KR, Abbott B, Hankinson O. ARNT-Deficient mice and placental differentiation. Dev. Biol. 191(2), 297-305 (1997
20. Ferrara N, Carver-Moore K, Chen H et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380(6573), 439-442 (1996
21. Maltepe E, Schmidt JV, Baunoch D, Bradfield CA, Simon MC. Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nature 386(6623), 403-407 (1997
22. Boyer LA, Mathur D, Jaenisch R. Molecular control of pluripotency. Curr. Opin. Genet. Dev. 16(5), 455-462 (2006
23. Panopoulos AD, Yanes O, Ruiz S et al. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res. 22(1), 168-177 (2012
24. Boyer LA, Plath K, Zeitlinger J et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441(7091), 349-353 (2006
25. Kashyap V, Rezende NC, Scotland KB et al. Regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the NANOG, OCT4, and SOX2 pluripotency transcription factors with polycomb repressive complexes and stem cell microRNAs. Stem Cells Dev. 18(7), 1093-1108 (2009
26. Ezashi T, Das P, Roberts RM. Low O2 tensions and the prevention of differentiation of hES cells. Proc. Natl Acad. Sci. USA 102(13), 4783-4788 (2005
27. Badger JL, Byrne ML, Veraitch FS, Mason C, Wall IB, Caldwell MA. Hypoxic culture of human pluripotent stem cell lines is permissible using mouse embryonic fibroblasts. Regen. Med. 7(5), 675-683 (2012
28. Westfall SD, Sachdev S, Das P et al. Identification of oxygen-sensitive transcriptional programs in human embryonic stem cells. Stem Cells Dev. 17(5), 869-881 (2008
29. Chen HF, Kuo HC, Chen W, Wu FC, Yang YS, Ho HN. A reduced oxygen tension (5%) is not beneficial for maintaining human embryonic stem cells in the undifferentiated state with short splitting intervals. Hum. Reprod. 24(1), 71-80 (2009
30. Ji L, Liu YX, Yang C et al. Self-renewal and pluripotency is maintained in human embryonic stem cells by co-culture with human fetal liver stromal cells expressing hypoxia inducible factor 1alpha. J. Cell. Physiol. 221(1), 54-66 (2009
31. Covello KL, Kehler J, Yu H et al. HIF 2alpha regulates Oct-4: Effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev. 20(5), 557-570 (2006
32. Moreno-Manzano V, Rodriguez-Jimenez FJ, Acena-Bonilla JL et al. FM19G11, a new hypoxia-inducible factor (HIF) modulator, affects stem cell differentiation status. J. Biol. Chem. 285(2), 1333-1342 (2010
33. Foja S, Jung M, Harwardt B, Riemann D, Pelz-Ackermann O, Schroeder IS. Hypoxia supports reprogramming of mesenchymal stromal cells via induction of embryonic stem cell-specific microRNA-302 cluster and pluripotency-Associated genes. Cell. Reprogram. 15(1), 68-79 (2013
34. Folmes CD, Nelson TJ, Martinez-Fernandez A et al. Somatic oxidative bioenergetics transitions into pluripotency-Dependent glycolysis to facilitate nuclear reprogramming. Cell Metab. 14(2), 264-271 (2011
35. Kondoh H, Lleonart ME, Nakashima Y et al. A high glycolytic flux supports the proliferative potential of murine embryonic stem cells. Antioxid. Redox Signal. 9(3), 293-299 (2007
36. Prigione A, Fauler B, Lurz R, Lehrach H, Adjaye J. The senescence-related mitochondrial/oxidative stress pathway is repressed in human induced pluripotent stem cells. Stem Cells 28(4), 721-733 (2010
37. Jeong CH, Lee HJ, Cha JH et al. Hypoxia-inducible factor-1 alpha inhibits self-renewal of mouse embryonic stem cells in vitro via negative regulation of the leukemia inhibitory factor-STAT3 pathway. J. Biol. Chem. 282(18), 13672-13679 (2007
38. Fernandes TG, Diogo MM, Fernandes-Platzgummer A, da Silva CL, Cabral JM. Different stages of pluripotency determine distinct patterns of proliferation, metabolism, and lineage commitment of embryonic stem cells under hypoxia. Stem Cell Res. 5(1), 76-89 (2010
39. Daheron L, Opitz SL, Zaehres H et al. LIF/ STAT3 signaling fails to maintain self-renewal of human embryonic stem cells. Stem Cells 22(5), 770-778 (2004
40. Yoshida Y, Takahashi K, Okita K, Ichisaka T, Yamanaka S. Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell 5(3), 237-241 (2009
41. Shimada H, Hashimoto Y, Nakada A, Shigeno K, Nakamura T. Accelerated generation of human induced pluripotent stem cells with retroviral transduction and chemical inhibitors under physiological hypoxia. Biochem. Biophys. Res. Commun. 417(2), 659-664 (2012
42. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4), 663-676 (2006
43. Takahashi K, Tanabe K, Ohnuki M et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5), 861-872 (2007
44. Yu J, Vodyanik MA, Smuga-Otto K et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858), 1917-1920 (2007
45. Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M. Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc. Jpn Acad. Ser. B Phys. Biol. Sci. 85(8), 348-362 (2009
46. Yun Z, Maecker HL, Johnson RS, Giaccia AJ. Inhibition of PPAR gamma 2 gene expression by the HIF 1-regulated gene DEC1/Stra13: A mechanism for regulation of adipogenesis by hypoxia. Dev. Cell 2(3), 331-341 (2002
47. Lee SW, Jeong HK, Lee JY et al. Hypoxic priming of mESCs accelerates vascular-lineage differentiation through HIF1-mediated inverse regulation of Oct4 and VEGF. EMBO Mol. Med. 4(9), 924-938 (2012
48. Ramirez-Bergeron DL, Runge A, Dahl KD, Fehling HJ, Keller G, Simon MC. Hypoxia affects mesoderm and enhances hemangioblast specification during early development. Development 131(18), 4623-4634 (2004
49. Niebruegge S, Bauwens CL, Peerani R et al. Generation of human embryonic stem cell-Derived mesoderm and cardiac cells using size-specified aggregates in an oxygen-controlled bioreactor. Biotechnol. Bioeng. 102(2), 493-507 (2009
50. Bae D, Mondragon-Teran P, Hernandez D et al. Hypoxia enhances the generation of retinal progenitor cells from human induced pluripotent and embryonic stem cells. Stem Cells Dev. 21(8), 1344-1355 (2012
51. Prado-Lopez S, Conesa A, Arminan A et al. Hypoxia promotes efficient differentiation of human embryonic stem cells to functional endothelium. Stem Cells 28(3), 407-418 (2010
52. Koay EJ, Athanasiou KA. Hypoxic chondrogenic differentiation of human embryonic stem cells enhances cartilage protein synthesis and biomechanical functionality. Osteoarthr. Cartil. 16(12), 1450-1456 (2008
53. Zhao T, Zhang CP, Liu ZH et al. Hypoxia-Driven proliferation of embryonic neural stem/ progenitor cells-role of hypoxia-inducible transcription factor-1alpha. FEBS J. 275(8), 1824-1834 (2008
54. Rodrigues CA, Diogo MM, da Silva CL, Cabral JM. Hypoxia enhances proliferation of mouse embryonic stem cell-Derived neural stem cells. Biotechnol. Bioeng. 106(2), 260-270 (2010
55. Francis KR, Wei L. Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning. Cell Death Dis. 1, e22 (2010
56. Studer L, Csete M, Lee SH et al. Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J. Neurosci. 20(19), 7377-7383 (2000
57. Kim TS, Misumi S, Jung CG et al. Increase in dopaminergic neurons from mouse embryonic stem cell-Derived neural progenitor/stem cells is mediated by hypoxia inducible factor-1alpha. J. Neurosci. Res. 86(11), 2353-2362 (2008
58. Gatti RA, Meuwissen HJ, Allen HD, Hong R, Good RA. Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet 2(7583), 1366-1369 (1968
59. Bortin MM. A compendium of reported human bone marrow transplants. Transplantation 9(6), 571-587 (1970
60. Tyndall A, Gratwohl A. Haemopoietic stem and progenitor cells in the treatment of severe autoimmune diseases. Ann. Rheum. Dis. 55(3), 149-151 (1996
61. Gratwohl A, Passweg J, Bocelli-Tyndall C et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases. Bone Marrow Transplant. 35(9), 869-879 (2005
62. Zhang J, Niu C, Ye L et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425(6960), 836-841 (2003
63. Parmar K, Mauch P, Vergilio JA, Sackstein R, Down JD. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc. Natl Acad. Sci. USA 104(13), 5431-5436 (2007
64. Brunet De La Grange P, Vlaski M, Duchez P et al. Long-Term repopulating hematopoietic stem cells and side population in human steady state peripheral blood. Stem Cell Res. 11(1), 625-633 (2013
65. Eliasson P, Jonsson JI. The hematopoietic stem cell niche: Low in oxygen but a nice place to be. J. Cell. Physiol. 222(1), 17-22 (2010
66. Kubota Y, Takubo K, Suda T. Bone marrow long label-retaining cells reside in the sinusoidal hypoxic niche. Biochem. Biophys. Res. Commun. 366(2), 335-339 (2008
67. Winkler IG, Barbier V, Wadley R, Zannettino AC, Williams S, Levesque JP. Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: Serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches. Blood 116(3), 375-385 (2010
68. Jang YY, Sharkis SJ. A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 110(8), 3056-3063 (2007
69. Lekli I, Gurusamy N, Ray D, Tosaki A, Das DK. Redox regulation of stem cell mobilization. Can. J. Physiol. Pharmacol. 87(12), 989-995 (2009
70. Danet GH, Pan Y, Luongo JL, Bonnet DA, Simon MC. Expansion of human SCID-repopulating cells under hypoxic conditions. J. Clin. Invest. 112(1), 126-135 (2003
71. Hermitte F, Brunet De La Grange P, Belloc F, Praloran V, Ivanovic Z. Very low O2 concentration (0.1%) favors G0 return of dividing CD34+ cells. Stem Cells 24(1), 65-73 (2006
72. Levesque JP, Winkler IG, Hendy J et al. Hematopoietic progenitor cell mobilization results in hypoxia with increased hypoxia-inducible transcription factor-1 alpha and vascular endothelial growth factor A in bone marrow. Stem Cells 25(8), 1954-1965 (2007
73. Piccoli C, DAprile A, Ripoli M et al. The hypoxia-inducible factor is stabilized in circulating hematopoietic stem cells under normoxic conditions. FEBS Lett. 581(16), 3111-3119 (2007
74. Simsek T, Kocabas F, Zheng J et al. The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell 7(3), 380-390 (2010
75. Pedersen M, Lofstedt T, Sun J, Holmquist-Mengelbier L, Pahlman S, Ronnstrand L. Stem cell factor induces HIF 1alpha at normoxia in hematopoietic cells. Biochem. Biophys. Res. Commun. 377(1), 98-103 (2008
76. Du J, Chen Y, Li Q et al. HIF 1alpha deletion partially rescues defects of hematopoietic stem cell quiescence caused by Cited2 deficiency. Blood 119(12), 2789-2798 (2012
77. Naka K, Muraguchi T, Hoshii T, Hirao A. Regulation of reactive oxygen species and genomic stability in hematopoietic stem cells. Antioxid. Redox Signal. 10(11), 1883-1894 (2008
78. Forristal CE, Winkler IG, Nowlan B, Barbier V, Walkinshaw G, Levesque JP. Pharmacologic stabilization of HIF 1alpha increases hematopoietic stem cell quiescence in vivo and accelerates blood recovery after severe irradiation. Blood 121(5), 759-769 (2013
79. Duchez P, Chevaleyre J, Brunet De La Grange P, Vlaski M, Boiron JM, Ivanovic Z. Functional stability (at +4 degrees C) of hematopoietic stem and progenitor cells amplified ex vivo from cord blood CD34(+) cells. Cell Transplant. 22(8), 1501-1506 (2013
80. Ivanovic Z, Duchez P, Chevaleyre J et al. Clinical-scale cultures of cord blood CD34(+) cells to amplify committed progenitors and maintain stem cell activity. Cell Transplant. 20(9), 1453-1463 (2011
81. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276(5309), 71-74 (1997
82. DIppolito G, Diabira S, Howard GA, Roos BA, Schiller PC. Low oxygen tension inhibits osteogenic differentiation and enhances stemness of human MIAMI cells. Bone 39(3), 513-522 (2006
83. Charles PG, Grayson ML. Point-of-care tests for lower respiratory tract infections. Med. J. Aust. 187(1), 36-39 (2007
84. Iwase T, Nagaya N, Fujii T et al. Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia. Cardiovasc. Res. 66(3), 543-551 (2005
85. Pittenger MF, Martin BJ. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ. Res. 95(1), 9-20 (2004
86. Choudry FA, Mathur A. Stem cell therapy in cardiology. Regen. Med. 6(6 Suppl.), 17-23 (2011
87. Wang CY, Yang HB, Hsu HS et al. Mesenchymal stem cell-conditioned medium facilitates angiogenesis and fracture healing in diabetic rats. J. Tissue Eng. Regen. Med. 6(7), 559-569 (2012
88. Ohnishi S, Yasuda T, Kitamura S, Nagaya N. Effect of hypoxia on gene expression of bone marrow-Derived mesenchymal stem cells and mononuclear cells. Stem Cells 25(5), 1166-1177 (2007
89. Tsai CC, Yew TL, Yang DC, Huang WH, Hung SC. Benefits of hypoxic culture on bone marrow multipotent stromal cells. Am. J. Blood Res. 2(3), 148-159 (2012
90. Crisostomo PR, Wang Y, Markel TA, Wang M, Lahm T, Meldrum DR. Human mesenchymal stem cells stimulated by TNF-Alpha, LPS, or hypoxia produce growth factors by an NF kappa B-but not JNK-Dependent mechanism. Am. J. Physiol. Cell Physiol. 294(3), C675-C682 (2008
91. Rosova I, Dao M, Capoccia B, Link D, Nolta JA. Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells 26(8), 2173-2182 (2008
92. Ceradini DJ, Kulkarni AR, Callaghan MJ et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF 1 induction of SDF-1. Nat. Med. 10(8), 858-864 (2004
93. Martin-Rendon E, Hale SJ, Ryan D et al. Transcriptional profiling of human cord blood CD133+ and cultured bone marrow mesenchymal stem cells in response to hypoxia. Stem Cells 25(4), 1003-1012 (2007
94. Dos Santos F, Andrade PZ, Boura JS, Abecasis MM, da Silva CL, Cabral JM. Ex vivo expansion of human mesenchymal stem cells: A more effective cell proliferation kinetics and metabolism under hypoxia. J. Cell. Physiol. 223(1), 27-35 (2010
95. Jin Y, Kato T, Furu M et al. Mesenchymal stem cells cultured under hypoxia escape from senescence via down-regulation of p16 and extracellular signal regulated kinase. Biochem. Biophys. Res. Commun. 391(3), 1471-1476 (2010
96. Deschepper M, Oudina K, David B et al. Survival and function of mesenchymal stem cells (MSCs) depend on glucose to overcome exposure to long-Term, severe and continuous hypoxia. J. Cell. Mol. Med. 15(7), 1505-1514 (2011
97. Yun SP, Lee MY, Ryu JM, Song CH, Han HJ. Role of HIF 1alpha and VEGF in human mesenchymal stem cell proliferation by 17beta-estradiol: Involvement of PKC, PI3K/Akt, and MAPKs. Am. J. Physiol. Cell Physiol. 296(2), C317-326 (2009
98. Huang F, Zhu X, Hu XQ et al. Mesenchymal stem cells modified with miR-126 release angiogenic factors and activate Notch ligand Delta-like-4, enhancing ischemic angiogenesis and cell survival. Int. J. Mol. Med. 31(2), 484-492 (2013
99. Tsai CC, Su PF, Huang YF, Yew TL, Hung SC. Oct4 and Nanog directly regulate Dnmt1 to maintain self-renewal and undifferentiated state in mesenchymal stem cells. Mol. Cell 47(2), 169-182 (2012
100. Kim J, Ma T. Autocrine fibroblast growth factor 2-mediated interactions between human mesenchymal stem cells and the extracellular matrix under varying oxygen tension. J. Cell. Biochem. 114(3), 716-727 (2013
101. Amarilio R, Viukov SV, Sharir A, Eshkar-Oren I, Johnson RS, Zelzer E. HIF1alpha regulation of Sox9 is necessary to maintain differentiation of hypoxic prechondrogenic cells during early skeletogenesis. Development 134(21), 3917-3928 (2007
102. Kanichai M, Ferguson D, Prendergast PJ, Campbell VA. Hypoxia promotes chondrogenesis in rat mesenchymal stem cells: A role for AKT and hypoxia-inducible factor (HIF)-1alpha. J. Cell. Physiol. 216(3), 708-715 (2008
103. Adesida AB, Mulet-Sierra A, Jomha NM. Hypoxia mediated isolation and expansion enhances the chondrogenic capacity of bone marrow mesenchymal stromal cells. Stem Cell Res. Ther. 3(2), 9 (2012
104. Duval E, Bauge C, Andriamanalijaona R et al. Molecular mechanism of hypoxia-induced chondrogenesis and its application in in vivo cartilage tissue engineering. Biomaterials 33(26), 6042-6051 (2012
105. Floyd ZE, Kilroy G, Wu X, Gimble JM. Effects of prolyl hydroxylase inhibitors on adipogenesis and hypoxia inducible factor 1 alpha levels under normoxic conditions. J. Cell. Biochem. 101(6), 1545-1557 (2007
106. Potier E, Ferreira E, Andriamanalijaona R et al. Hypoxia affects mesenchymal stromal cell osteogenic differentiation and angiogenic factor expression. Bone 40(4), 1078-1087 (2007
107. Xu N, Liu H, Qu F et al. Hypoxia inhibits the differentiation of mesenchymal stem cells into osteoblasts by activation of Notch signaling. Exp. Mol. Pathol. 94(1), 33-39 (2013
108. Benjamin S, Sheyn D, Ben-David S et al. Oxygenated environment enhances both stem cell survival and osteogenic differentiation. Tissue Eng. Part A 19(5-6), 748-758 (2013
109. Erecinska M, Silver IA. Tissue oxygen tension and brain sensitivity to hypoxia. Respir. Physiol. 128(3), 263-276 (2001
110. Laywell ED, Steindler DA, Silver DJ. Astrocytic stem cells in the adult brain. Neurosurg. Clin. N. Am. 18(1), 21-30, viii (2007
111. Alvarez-Buylla A, Garcia-Verdugo JM. Neurogenesis in adult subventricular zone. J. Neurosci. 22(3), 629-634 (2002
112. Tavazoie M, Van Der Veken L, Silva-Vargas V et al. A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3(3), 279-288 (2008
113. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97(6), 703-716 (1999
114. Lopez-Barneo J, Pardal R, Ortega-Saenz P, Duran R, Villadiego J, Toledo-Aral JJ. The neurogenic niche in the carotid body and its applicability to antiparkinsonian cell therapy. J. Neural Transm. 116(8), 975-982 (2009
115. Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol. Cell 40(2), 294-309 (2010
116. Fujiwara K, Date I, Shingo T et al. Neurotrophic factor-secreting cell grafting for cerebral ischemia: Preliminary report. Cell Transplant. 10(4-5), 419-422 (2001
117. Chavali PL, Saini RK, Matsumoto Y, Agren H, Funa K. Nuclear orphan receptor TLX induces Oct-3/4 for the survival and maintenance of adult hippocampal progenitors upon hypoxia. J. Biol. Chem. 286(11), 9393-9404 (2011
118. Zeng ZJ, Johansson E, Hayashi A et al. TLX controls angiogenesis through interaction with the von Hippel-Lindau protein. Biol. Open 1(6), 527-535 (2012
119. Kokovay E, Goderie S, Wang Y et al. Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling. Cell Stem Cell 7(2), 163-173 (2010
120. Gustafsson MV, Zheng X, Pereira T et al. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev. Cell 9(5), 617-628 (2005
121. Liu YV, Baek JH, Zhang H, Diez R, Cole RN, Semenza GL. RACK1 competes with HSP90 for binding to HIF 1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF 1alpha. Mol. Cell 25(2), 207-217 (2007
122. Mazumdar J, OBrien WT, Johnson RS et al. O2 regulates stem cells through Wnt/beta-catenin signalling. Nat. Cell Biol. 12(10), 1007-1013 (2010
123. Arai K, Lo EH. Astrocytes protect oligodendrocyte precursor cells via MEK/ERK and PI3K/Akt signaling. J. Neurosci. Res. 88(4), 758-763 (2010
124. Sung SM, Jung DS, Kwon CH, Park JY, Kang SK, Kim YK. Hypoxia/ reoxygenation stimulates proliferation through PKC-Dependent activation of ERK and Akt in mouse neural progenitor cells. Neurochem. Res. 32(11), 1932-1939 (2007
125. Chen X, Tian Y, Yao L, Zhang J, Liu Y. Hypoxia stimulates proliferation of rat neural stem cells with influence on the expression of cyclin D1 and c-Jun N-Terminal protein kinase signaling pathway in vitro. Neuroscience 165(3), 705-714 (2010
126. Santilli G, Lamorte G, Carlessi L et al. Mild hypoxia enhances proliferation and multipotency of human neural stem cells. PloS ONE 5(1), e8575 (2010
127. Stoll EA, Cheung W, Mikheev AM et al. Aging neural progenitor cells have decreased mitochondrial content and lower oxidative metabolism. J. Biol. Chem. 286(44), 38592-38601 (2011
128. Zhu LL, Zhao T, Huang X et al. Gene expression profiles and metabolic changes in embryonic neural progenitor cells under low oxygen. Cell. Reprogram. 13(2), 113-120 (2011
129. Reekmans K, Praet J, Daans J et al. Current challenges for the advancement of neural stem cell biology and transplantation research. Stem Cell Rev. 8(1), 262-278 (2012
130. De Feo D, Merlini A, Laterza C, Martino G. Neural stem cell transplantation in central nervous system disorders: From cell replacement to neuroprotection. Curr. Opin. Neurol. 25(3), 322-333 (2012