Transcriptome-based chemical screens identify CDK8 as a common barrier in multiple cell reprogramming systems

• DOI: 10.1016/j.celrep.2023.112566
• Publication Date: 2023-05-24T21:39:09Z
• Authors: Jun Li; Yunfei Bai; Yang Liu; Zhongya Song; Yong Yang; Yang Zhao
• Keywords: Reprogramming; Cell fate determination

Fibroblasts can be chemically induced to pluripotent stem cells (CiPSCs) through an extraembryonic endoderm (XEN)-like state or directly converted into other differentiated cell lineages. However, the mechanisms underlying cell-fate reprogramming remain unclear. Here, a transcriptome-based screen of biologically active compounds uncovered that CDK8 inhibition was essential enable from fibroblasts XEN-like cells, then CiPSCs. RNA-sequencing analysis showed downregulated proinflammatory pathways suppress chemical and facilitated induction multi-lineage priming state, indicating establishment plasticity in fibroblasts. also resulted chromatin accessibility profile like under initial reprogramming. Moreover, greatly promoted mouse hepatocyte-like human adipocytes. These collective findings thus highlight as general molecular barrier multiple processes, common target for inducing fate conversion.