Séguin Cheryle A, Draper Jonathan S, Nagy Andras, Rossant Janet
The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON M5G 1L7, Canada.
Cell Stem Cell. 2008 Aug 7;3(2):182-95. doi: 10.1016/j.stem.2008.06.018.
In this study, we explore endoderm cell fate regulation through the expression of lineage-determining transcription factors. We demonstrate that stable endoderm progenitors can be established from human ES cells by constitutive expression of SOX7 or SOX17, producing extraembryonic endoderm and definitive endoderm progenitors, respectively. In teratoma assays and growth factor-mediated differentiation, SOX7 cells appear restricted to the extraembryonic endoderm, and SOX17 cells demonstrate a mesendodermal phenotype in teratomas and the ability to undergo endoderm maturation in vitro in the absence of cytokine-mediated endoderm induction. These endoderm progenitor cells maintain a stable phenotype through many passages in culture, thereby providing new tools to explore the pathways of endoderm differentiation.
在本研究中,我们通过谱系决定转录因子的表达来探索内胚层细胞命运调控。我们证明,通过组成型表达SOX7或SOX17,可以从人胚胎干细胞建立稳定的内胚层祖细胞,分别产生胚外内胚层和定形内胚层祖细胞。在畸胎瘤试验和生长因子介导的分化中,SOX7细胞似乎局限于胚外内胚层,而SOX17细胞在畸胎瘤中表现出中内胚层表型,并且在没有细胞因子介导的内胚层诱导的情况下能够在体外进行内胚层成熟。这些内胚层祖细胞在培养中经过多次传代仍保持稳定的表型,从而为探索内胚层分化途径提供了新工具。