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10.1016/j.cell.2022.11.026

http://scihub22266oqcxt.onion/10.1016/j.cell.2022.11.026
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suck abstract from ncbi

pmid36608654      Cell 2023 ; 186 (1): 209-229.e26
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  • A transcription factor atlas of directed differentiation #MMPMID36608654
  • Joung J; Ma S; Tay T; Geiger-Schuller KR; Kirchgatterer PC; Verdine VK; Guo B; Arias-Garcia MA; Allen WE; Singh A; Kuksenko O; Abudayyeh OO; Gootenberg JS; Fu Z; Macrae RK; Buenrostro JD; Regev A; Zhang F
  • Cell 2023[Jan]; 186 (1): 209-229.e26 PMID36608654show ga
  • Transcription factors (TFs) regulate gene programs, thereby controlling diverse cellular processes and cell states. To comprehensively understand TFs and the programs they control, we created a barcoded library of all annotated human TF splice isoforms (>3,500) and applied it to build a TF Atlas charting expression profiles of human embryonic stem cells (hESCs) overexpressing each TF at single-cell resolution. We mapped TF-induced expression profiles to reference cell types and validated candidate TFs for generation of diverse cell types, spanning all three germ layers and trophoblasts. Targeted screens with subsets of the library allowed us to create a tailored cellular disease model and integrate mRNA expression and chromatin accessibility data to identify downstream regulators. Finally, we characterized the effects of combinatorial TF overexpression by developing and validating a strategy for predicting combinations of TFs that produce target expression profiles matching reference cell types to accelerate cellular engineering efforts.
  • |*Cell Differentiation[MESH]
  • |*Transcription Factors/metabolism[MESH]
  • |Atlases as Topic[MESH]
  • |Chromatin[MESH]
  • |Gene Expression Regulation[MESH]
  • |Human Embryonic Stem Cells/metabolism[MESH]


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