A small molecule inhibitor of SRC family kinases promotes simple epithelial differentiation of human pluripotent stem cells.
A small molecule inhibitor of SRC family kinases promotes simple epithelial differentiation of human pluripotent stem cells.
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DOI：
10.1371/journal.pone.0060016
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Palecek SP
中科院分区：
文献类型：
--
作者：
Lian X;Selekman J;Bao X;Hsiao C;Zhu K;Palecek SP
人类多能干细胞(HPSCs)为体外研究人类早期发育提供了前所未有的机会，并有可能为再生医学提供无限的新细胞来源。虽然以前的研究报道了hPSC产生细胞角蛋白14+/p63+角质形成细胞，但尚未描述上皮细胞系的多潜能前体细胞，而且调控上皮细胞承诺的发育途径在很大程度上仍不清楚。在此，我们报道了β-连环蛋白在维甲酸(RA)诱导的上皮分化过程中的膜定位。此外，在特定的培养条件下，用src家族激酶抑制剂SU6656处理hPSC可以调节β-连环蛋白的定位，并产生丰富的简单上皮细胞群。SU6656强烈上调在单纯上皮细胞中表达的细胞角蛋白18和8(K18/K8)的表达，同时抑制多能基因Oct4的表达。这种同质的K18+K8+Oct4−简单上皮前体细胞群可以进一步分化为表达角质形成细胞或角膜特异性标志物的细胞。这些富含hPSC来源的简单上皮细胞可能为发展和毒理学细胞模型提供现成的来源，并可能作为上皮细胞移植应用的前体细胞。
Human pluripotent stem cells (hPSCs) provide unprecedented opportunities to study the earliest stages of human development in vitro and have the potential to provide unlimited new sources of cells for regenerative medicine. Although previous studies have reported cytokeratin 14+/p63+ keratinocyte generation from hPSCs, the multipotent progenitors of epithelial lineages have not been described and the developmental pathways regulating epithelial commitment remain largely unknown. Here we report membrane localization of β-catenin during retinoic acid (RA) – induced epithelial differentiation. In addition hPSC treatment with the Src family kinase inhibitor SU6656 modulated β-catenin localization and produced an enriched population of simple epithelial cells under defined culture conditions. SU6656 strongly upregulated expression of cytokeratins 18 and 8 (K18/K8), which are expressed in simple epithelial cells, while repressing expression of the pluripotency gene Oct4. This homogeneous population of K18+K8+Oct4− simple epithelial precursor cells can further differentiate into cells expressing keratinocyte or corneal-specific markers. These enriched hPSC-derived simple epithelial cells may provide a ready source for development and toxicology cell models and may serve as a progenitor for epithelial cell transplantation applications.
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影响因子：
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作者：
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通讯作者：
Roop, Dennis R.
影响因子：
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