Simulated microgravity promoted differentiation of bipotential murine oval liver stem cells by modulating BMP4/notch1 signaling
Simulated microgravity promoted differentiation of bipotential murine oval liver stem cells by modulating BMP4/notch1 signaling
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DOI：
10.1002/jcb.23110
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发表时间：
2011-07
影响因子：
4
通讯作者：
Syamantak Majumder;J. Siamwala;Sundaramoorthy M. Srinivasan;Swaraj Sinha;S. C. Sridhara;G. Soundararajan;H. Seerapu;S. Chatterjee
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作者：
Syamantak Majumder;J. Siamwala;Sundaramoorthy M. Srinivasan;Swaraj Sinha;S. C. Sridhara;G. Soundararajan;H. Seerapu;S. Chatterjee
肝干细胞的快速生长和向肝细胞分化是肝再生的关键因素之一。近年来，模拟微重力，一种物理力已经显示出差异调节干细胞的分化和增殖。本文研究了模拟微重力对肝干细胞分化和增殖的影响。细胞受到微重力，这是模拟使用本土制造的3D回转器。采用增殖、凋亡、免疫荧光和Western blot等方法研究模拟微重力对肝干细胞的影响。微重力处理2 h可使干细胞增殖增加两倍，而不诱导凋亡和损害细胞活力。对微重力处理2 h后肝细胞核因子4-α（HNF 4-α）表达的分析表明，单独微重力可在2-3天内诱导干细胞分化。在微重力处理的干细胞中探测骨形态发生蛋白4（BMP 4）和Notch 1，阐述了孵育2天后Notch 1的下调和BMP 4的上调。此外，使用来自脊索蛋白质粒转染的细胞的dorsomorphin和脊索蛋白条件培养基阻断BMP 4减弱了微重力介导的肝干细胞分化。总之，微重力与干细胞中的BMP 4/Notch 1信号相互作用，从而诱导干细胞分化为肝细胞。目前的研究结果可能涉及临床研究，其中微重力激活的干细胞可以在肝损伤后有效地再生肝脏。J.细胞。112：1898-1908，2011.© 2011 Wiley利斯公司
Faster growth and differentiation of liver stem cells to hepatocyte is one of the key factors during liver regeneration. In recent years, simulated microgravity, a physical force has shown to differentially regulate the differentiation and proliferation of stem cells. In the present work, we studied the effect of simulated microgravity on differentiation and proliferation of liver stem cells. The cells were subjected to microgravity, which was simulated using indigenously fabricated 3D clinostat. Proliferation, apoptosis, immunofluorescence assays and Western blot analysis were carried out to study the effects of simulated microgravity on liver stem cells. Microgravity treatment for 2 h enhanced proliferation of stem cells by twofold without inducing apoptosis and compromising cell viability. Analysis of hepatocyte nuclear factor 4‐α (HNF4‐α) expression after 2 h of microgravity treatment revealed that microgravity alone can induce the differentiation of stem cells within 2–3 days. Probing bone morphogenic protein 4 (BMP4) and Notch1 in microgravity treated stem cells elaborated downregulation of Notch1 and upregulation of BMP4 after 2 days of incubation. Further, blocking BMP4 using dorsomorphin and chordin conditioned media from chordin plasmid transfected cells attenuated microgravity mediated differentiation of liver stem cells. In conclusion, microgravity interplays with BMP4/Notch1 signaling in stem cells thus inducing differentiation of stem cells to hepatocytes. Present findings can be implicated in clinical studies where microgravity activated stem cells can regenerate the liver efficiently after liver injury. J. Cell. Biochem. 112: 1898–1908, 2011. © 2011 Wiley‐Liss, Inc.