TY - JOUR T1 - Responsiveness to perturbations is a hallmark of transcription factors that maintain cell identity JF - bioRxiv DO - 10.1101/2020.06.11.147207 SP - 2020.06.11.147207 AU - Ian A. Mellis AU - Hailey I. Edelstein AU - Rachel Truitt AU - Lauren E. Beck AU - Orsolya Symmons AU - Yogesh Goyal AU - Margaret C. Dunagin AU - Ricardo A. Linares Saldana AU - Parisha P. Shah AU - Wenli Yang AU - Rajan Jain AU - Arjun Raj Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/06/30/2020.06.11.147207.abstract N2 - Our ability to identify the particular transcription factors that maintain cell type is limited. Identification of factors by their cell type-specific expression or their participation in developmental regulation has been only modestly successful. We hypothesized that because cell type is often resilient to perturbations, the transcriptional response to perturbations would identify identity-maintaining factors. We developed Perturbation Panel Profiling (P3) as a framework for perturbing cells in dozens of conditions and measuring gene expression responsiveness transcriptome-wide. Applying P3 to human iPSC-derived cardiac myocytes showed that transcription factors known to function in cardiac differentiation and maintenance were among the most frequently up-regulated (most responsive). We reasoned that one potential function of responsive genes may be to maintain cellular identity. We identified responsive transcription factors in fibroblasts using P3 and found that suppressing their expression led to enhanced reprogramming efficiency. We propose that responsiveness to perturbations is a property of factors that help maintain cellular identity.Competing Interest StatementAR receives patent royalties from LGC/Biosearch Technologies related to Stellaris RNA FISH probes. ER -