Gata6 potently initiates reprograming of pluripotent and differentiated cells to extraembryonic endoderm stem cells
Publication in refereed journal


摘要Transcription factor-mediated reprograming is a powerful method to study cell fate changes. In this study, we demonstrate that the transcription factor Gata6 can initiate reprograming of multiple cell types to induced extraembryonic endoderm stem (iXEN) cells. Intriguingly, Gata6 is sufficient to drive iXEN cells frommouse pluripotent cells and differentiated neural cells. Furthermore, GATA6 induction in human embryonic stem (hES) cells also down-regulates pluripotency gene expression and up-regulates extraembryonic endoderm (ExEn) genes, revealing a conserved function in mediating this cell fate switch. Profiling transcriptional changes following Gata6 induction in mES cells reveals step-wise pluripotency factor disengagement, with initial repression of Nanog and Esrrb, then Sox2, and finally Oct4, alongside step-wise activation of ExEn genes. Chromatin immunoprecipitation and subsequent high-throughput sequencing analysis shows Gata6 enrichment near pluripotency and endoderm genes, suggesting that Gata6 functions as both a direct repressor and activator. Together, this demonstrates that Gata6 is a versatile and potent reprograming factor that can act alone to drive a cell fate switch from diverse cell types.
著者Wamaitha S.E., del Valle I., Cho L.T.Y., Wei Y., Fogarty N.M.E., Blakeley P., Sherwood R.I., Ji H., Niakan K.K.
期刊名稱Genes and Development
出版社Cold Spring Harbor Laboratory Press
出版地United States
頁次1239 - 1255
關鍵詞Extraembryonic endoderm, Gata6, Human embryonic stem cells, Mouse embryonic stem cells, Pluripotency, Reprograming

上次更新時間 2021-27-02 於 01:52