Gata6 potently initiates reprograming of pluripotent and differentiated cells to extraembryonic endoderm stem cells
journal contributionposted on 22.09.2020, 11:37 authored by Sissy E Wamaitha, Ignacio Del Valle, Lily TY Cho, Yingying Wei, Norah ME Fogarty, Paul Blakeley, Richard I Sherwood, Hongkai Ji, Kathy K Niakan
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 from mouse 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.
Gata6extraembryonic endodermhuman embryonic stem cellsmouse embryonic stem cellspluripotencyreprogramingAnimalsBinding SitesCell DifferentiationCellular ReprogrammingEmbryonic Stem CellsEndodermFibroblast Growth Factor 4GATA4 Transcription FactorGATA6 Transcription FactorGene Expression Regulation, DevelopmentalGene Regulatory NetworksHumansMiceOctamer Transcription Factor-3Pluripotent Stem CellsProtein BindingSignal TransductionNiakan MC_UP_1202/9AS-ackBRF-ackLM-ack06 Biological Sciences11 Medical and Health Sciences17 Psychology and Cognitive SciencesDevelopmental Biology