Sox17介导的XEN细胞转化鉴定了控制胚胎干细胞中细胞命运决定的动态网络。
Sox17-mediated XEN cell conversion identifies dynamic networks controlling cell-fate decisions in embryo-derived stem cells.
作者信息
McDonald Angela C H, Biechele Steffen, Rossant Janet, Stanford William L
机构信息
Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada.
Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
出版信息
Cell Rep. 2014 Oct 23;9(2):780-93. doi: 10.1016/j.celrep.2014.09.026. Epub 2014 Oct 16.
Little is known about the gene regulatory networks (GRNs) distinguishing extraembryonic endoderm (ExEn) stem (XEN) cells from those that maintain the extensively characterized embryonic stem cell (ESC). An intriguing network candidate is Sox17, an essential transcription factor for XEN derivation and self-renewal. Here, we show that forced Sox17 expression drives ESCs toward ExEn, generating XEN cells that contribute to ExEn when placed back into early mouse embryos. Transient Sox17 expression is sufficient to drive this fate change during which time cells transit through distinct intermediate states prior to the generation of functional XEN-like cells. To orchestrate this conversion process, Sox17 acts in autoregulatory and feedforward network motifs, regulating dynamic GRNs directing cell fate. Sox17-mediated XEN conversion helps to explain the regulation of cell-fate changes and reveals GRNs regulating lineage decisions in the mouse embryo.
关于区分胚外内胚层（ExEn）干细胞（XEN）与那些已被广泛研究的胚胎干细胞（ESC）的基因调控网络（GRN），我们所知甚少。一个引人关注的网络候选因子是Sox17，它是XEN细胞衍生和自我更新所必需的转录因子。在此，我们表明，强制表达Sox17可促使ESC向ExEn分化，产生的XEN细胞在重新植入早期小鼠胚胎时可形成ExEn。短暂的Sox17表达足以驱动这种命运转变，在此期间，细胞在产生功能性类XEN细胞之前会经历不同的中间状态。为协调这一转化过程，Sox17在自动调节和前馈网络基序中发挥作用，调控指导细胞命运的动态GRN。Sox17介导的XEN转化有助于解释细胞命运变化的调控机制，并揭示了调控小鼠胚胎中谱系决定的GRN。
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