Department of Internal Medicine I, University of Ulm, Albert-Einstein Allee 23, 89081 Ulm, Germany.
Stem Cells Int. 2013;2013:360573. doi: 10.1155/2013/360573. Epub 2013 Apr 16.
Pluripotent stem cells present an extraordinary powerful tool to investigate embryonic development in humans. Essentially, they provide a unique platform for dissecting the distinct mechanisms underlying pluripotency and subsequent lineage commitment. Modest information currently exists about the expression and the role of ion channels during human embryogenesis, organ development, and cell fate determination. Of note, small and intermediate conductance, calcium-activated potassium channels have been reported to modify stem cell behaviour and differentiation. These channels are broadly expressed throughout human tissues and are involved in various cellular processes, such as the after-hyperpolarization in excitable cells, and also in differentiation processes. To this end, human induced pluripotent stem cells (hiPSCs) generated from plucked human hair keratinocytes have been exploited in vitro to recapitulate endoderm formation and, concomitantly, used to map the expression of the SK channel (SKCa) subtypes over time. Thus, we report the successful generation of definitive endoderm from hiPSCs of ectodermal origin using a highly reproducible and robust differentiation system. Furthermore, we provide the first evidence that SKCas subtypes are dynamically regulated in the transition from a pluripotent stem cell to a more lineage restricted, endodermal progeny.
多能干细胞为研究人类胚胎发育提供了一种非常强大的工具。它们本质上为解析多能性和随后的谱系分化背后的独特机制提供了一个独特的平台。目前关于离子通道在人类胚胎发生、器官发育和细胞命运决定过程中的表达和作用的信息有限。值得注意的是，小电导和中等电导钙激活钾通道已被报道可以改变干细胞的行为和分化。这些通道在人类组织中广泛表达，并参与各种细胞过程，如兴奋细胞中的后超极化，以及分化过程。为此，已在体外利用从拔出的人类毛发角蛋白细胞生成的人诱导多能干细胞 (hiPSC) 来重现内胚层形成，并同时用于随时间推移绘制 SK 通道 (SKCa) 亚型的表达图谱。因此，我们报告了使用高度可重复和稳健的分化系统，从外胚层来源的 hiPSC 成功生成确定的内胚层。此外，我们提供了第一个证据，表明 SKCa 亚型在从多能干细胞向更具谱系限制的内胚层后代的过渡过程中是动态调节的。
