Recent reports have proposed a new paradigm for obtaining mature somatic cell types from fibroblasts without going through a pluripotent state, by briefly expressing canonical iPSC reprogramming factors Oct4, Sox2, Klf4 and c-Myc (abbreviated as OSKM), in cells expanded in lineage differentiation promoting conditions. Here we apply genetic lineage tracing for endogenous Nanog, Oct4 and X chromosome reactivation during OSKM induced trans-differentiation, as these molecular events mark final stages for acquisition of induced pluripotency. Remarkably, the vast majority of reprogrammed cardiomyocytes or neural stem cells derived from mouse fibroblasts via OSKM mediated trans-differentiation were attained after transient acquisition of pluripotency, and followed by rapid differentiation. Our findings underscore a molecular and functional coupling between inducing pluripotency and obtaining trans-differentiated somatic cells via OSKM induction, and have implications on defining molecular trajectories assumed during different cell reprogramming methods. SOURCE: Noa Novershtern (noa.novershtern@weizmann.ac.il) -  Weizmann Institute of Science

Pluto Bioinformatics

GSE67265: Frequent and Transient Acquisition of Pluripotency During Somatic Cell Trans-Differentiation with iPSCs Reprogramming Factors (RNA-Seq)