Abstract:
:Ectopic expression of transcription factors (TFs) can reprogram cell state. However, because of the large combinatorial space of possible TF cocktails, it remains difficult to identify TFs that reprogram specific cell types. Here, we develop Reprogram-Seq to experimentally screen thousands of TF cocktails for reprogramming performance. Reprogram-Seq leverages organ-specific cell-atlas data with single-cell perturbation and computational analysis to predict, evaluate, and optimize TF combinations that reprogram a cell type of interest. Focusing on the cardiac system, we perform Reprogram-Seq on MEFs using an undirected library of 48 cardiac factors and, separately, a directed library of 10 epicardial-related TFs. We identify a combination of three TFs, which efficiently reprogram MEFs to epicardial-like cells that are transcriptionally, molecularly, morphologically, and functionally similar to primary epicardial cells. Reprogram-Seq holds promise to accelerate the generation of specific cell types for regenerative medicine.
journal_name
Cell Repjournal_title
Cell reportsauthors
Duan J,Li B,Bhakta M,Xie S,Zhou P,Munshi NV,Hon GCdoi
10.1016/j.celrep.2019.05.079subject
Has Abstractpub_date
2019-06-18 00:00:00pages
3486-3499.e6issue
12issn
2211-1247pii
S2211-1247(19)30708-9journal_volume
27pub_type
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