Hypoxic culture maintains self-renewal and enhances embryoid body formation of human embryonic stem cells

Hsin Fu Chen, Hung Chih Kuo, Shau Ping Lin, Chung Liang Chien, Ming Shan Chiang, Hong Nerng Ho

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33 引文 斯高帕斯(Scopus)


Hypoxic environment is theoretically more physiological for the growth of human embryonic stem (hES) cells. It has been reported that hypoxic culture maintained better undifferentiation of hES cells, but the effects on differentiation are less well established. The hES cells were thus cultured and compared in hypoxia (2% oxygen [O2]) and normoxia (21% O 2). The data showed that the undifferentiated state of hES cells was maintained more favorably in hypoxia during prolonged culture. Most tested genes belonging to FGF, TGF-β/GMP, and Wnt signaling pathways were enriched in undifferentiated hES cells and downregulated upon differentiation, accompanied with differential expression of FGFR1, FGFR2, and FRAT2 between hypoxia and normoxia. Higher P-Smad2/3 level was identified in hypoxia, favoring the maintenance of hES cells in undifferentiation. Bisulfite sequencing showed similar imprinting status between different O2 tensions at H19 differentially methylated region (DMR) and KvDMR loci. Embryoid body formation was enhanced in hypoxia accompanied with suppressed Sox17, Desmin, Gata4, Brachyury, and Cdx2 expression. We concluded that hypoxia improved self-renewal of hES cells through modulation of major signaling pathways and was also more efficient for differentiation to embryoid bodies, though they might present with suppressed expression of some lineage-specific genes across all the three embryonic germ layers and trophectoderm.
頁(從 - 到)2901-2913
期刊Tissue Engineering - Part A
出版狀態已發佈 - 9月 1 2010

ASJC Scopus subject areas

  • 生物工程
  • 生物化學
  • 生物材料
  • 生物醫學工程


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