A Src inhibitor regulates the cell cycle of human pluripotent stem cells and improves directed differentiation.
A Src inhibitor regulates the cell cycle of human pluripotent stem cells and improves directed differentiation.
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DOI：
10.1083/jcb.201502035
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发表时间：
2015-09-28
期刊：
影响因子：
--
通讯作者：
Melton DA
中科院分区：
文献类型：
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作者：
Chetty S;Engquist EN;Mehanna E;Lui KO;Tsankov AM;Melton DA
通过遗传抑制或小分子抑制剂PP1抑制Src活性增强了人多能干细胞在所有胚层中的分化能力，并且这些改善之前是多能细胞周期中视网膜母细胞瘤蛋白的激活。将人类多能干细胞（hPSC）驱动成特定谱系是一个低效且具有挑战性的过程。我们发现，一个有效的Src抑制剂，PP1，调节参与细胞周期的G1期到S期转变的基因的表达，激活视网膜母细胞瘤家族中的蛋白质，并随后增加hPSC分化为所有三个胚层的倾向。我们进一步证明，Src的遗传抑制调节视网膜母细胞瘤蛋白的活性，并增强hPSC在所有胚层中的分化潜力。这些积极的影响超出了最初的胚层特化，并能够在随后的分化阶段进行有效的分化。
Inhibiting Src activity through genetic suppression or the small molecule inhibitor PP1 enhances the differentiation capacity of human pluripotent stem cells across all germ layers, and these improvements are preceded by activation of the retinoblastoma protein in the pluripotent cell cycle. Driving human pluripotent stem cells (hPSCs) into specific lineages is an inefficient and challenging process. We show that a potent Src inhibitor, PP1, regulates expression of genes involved in the G1 to S phase transition of the cell cycle, activates proteins in the retinoblastoma family, and subsequently increases the differentiation propensities of hPSCs into all three germ layers. We further demonstrate that genetic suppression of Src regulates the activity of the retinoblastoma protein and enhances the differentiation potential of hPSCs across all germ layers. These positive effects extend beyond the initial germ layer specification and enable efficient differentiation at subsequent stages of differentiation.