Establishment of endoderm progenitors by SOX transcription factor expression in human embryonic stem cells

Establishment of endoderm progenitors by SOX transcription factor expression in human embryonic stem cells
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DOI:
10.1016/j.stem.2008.06.018
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发表时间:
2008-08-07
期刊:
影响因子:
23.9
通讯作者:
Rossant, Janet
Rossant, Janet
中科院分区:
医学1区
文献类型:
--
作者:
Seguin, Cheryle A.;Draper, Jonathan S.;Rossant, Janet

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在这项研究中,我们探讨内胚层细胞命运的调控,通过表达的谱系决定转录因子。我们证明,稳定的内胚层祖细胞可以建立从人ES细胞组成型表达的SOX 7或SOX 17,产生胚外内胚层和定形内胚层祖细胞,分别。在畸胎瘤测定和生长因子介导的分化中,SOX 7细胞似乎仅限于胚外内胚层,SOX 17细胞在畸胎瘤中表现出中内胚层表型,并且在没有苦参碱介导的内胚层诱导的情况下能够在体外经历内胚层成熟。这些内胚层祖细胞在培养中通过多次传代保持稳定的表型,从而为探索内胚层分化途径提供了新的工具。
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.