Gata6 potently initiates reprograming of pluripotent and differentiated cells to extraembryonic endoderm stem cells
| Autor: | Hongkai Ji, Paul Blakeley, Yingying Wei, Richard I. Sherwood, Kathy K. Niakan, Ignacio del Valle, Sissy E. Wamaitha, Norah M. E. Fogarty, Lily T. Y. Cho |
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| Rok vydání: | 2015 |
| Předmět: |
Pluripotent Stem Cells
Homeobox protein NANOG endocrine system animal structures Cellular differentiation Fibroblast Growth Factor 4 Biology Cell fate determination Mice SOX2 GATA6 Transcription Factor Genetics medicine Animals Humans Gene Regulatory Networks Induced pluripotent stem cell Embryonic Stem Cells Binding Sites fungi Endoderm Gene Expression Regulation Developmental Cell Differentiation Cellular Reprogramming Embryonic stem cell GATA4 Transcription Factor medicine.anatomical_structure embryonic structures Cancer research biological phenomena cell phenomena and immunity Stem cell Octamer Transcription Factor-3 Research Paper Protein Binding Signal Transduction Developmental Biology |
| Zdroj: | Genes & Development. 29:1239-1255 |
| ISSN: | 1549-5477 0890-9369 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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