A Systematic Approach to Identify Candidate Transcription Factors that Control Cell Identity

• Core transcription factors (TFs) are predicted for >200 cell types/tissues
• Predicted TFs for retinal pigment epithelial (RPE) cells can reprogram fibroblasts
• These reprogrammed RPE-like cells are functionally similar to primary RPE
• The sets of predicted factors may facilitate studies of control of cell identity

SummaryHundreds of transcription factors (TFs) are expressed in each cell type, but cell identity can be induced through the activity of just a small number of core TFs. Systematic identification of these core TFs for a wide variety of cell types is currently lacking and would establish a foundation for understanding the transcriptional control of cell identity in development, disease, and cell-based therapy. Here, we describe a computational approach that generates an atlas of candidate core TFs for a broad spectrum of human cells. The potential impact of the atlas was demonstrated via cellular reprogramming efforts where candidate core TFs proved capable of converting human fibroblasts to retinal pigment epithelial-like cells. These results suggest that candidate core TFs from the atlas will prove a useful starting point for studying transcriptional control of cell identity and reprogramming in many human cell types.

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