A transcription factor atlas of directed differentiation
Name
PIIS0092867422014702.pdf
Description
Published version
Size
16.05 MB
Format
Adobe PDF
Checksum (MD5)
0b119b43db022a772a576b8e2fbb430a
Author(s)
Joung, Julia
Ma, Sai
Tay, Tristan
Geiger-Schuller, Kathryn R
Kirchgatterer, Paul C
Verdine, Vanessa K
Guo, Baolin
Arias-Garcia, Mario A
Allen, William E
Singh, Ankita
Date Issued
January 2023
Journal
Cell
Publisher
Elsevier BV
Citation
Joung, Julia, Ma, Sai, Tay, Tristan, Geiger-Schuller, Kathryn R, Kirchgatterer, Paul C et al. 2023. "A transcription factor atlas of directed differentiation." Cell, 186 (1).
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2022.11.026
