PT  - JOURNAL ARTICLE
AU  - Itay Maza
AU  - Inbal Caspi
AU  - Sergey Viukov
AU  - Yoach Rais
AU  - Asaf Zviran
AU  - Shay Geula
AU  - Vladislav Krupalnik
AU  - Mirie Zerbib
AU  - Rada Massarwa
AU  - Noa Novershtern
AU  - Jacob H. Hanna
TI  - Frequent and Transient Acquisition of Pluripotency During Somatic Cell Trans-Differentiation with iPSC Reprogramming Factors
AID  - 10.1101/008284
DP  - 2014 Jan 01
TA  - bioRxiv
PG  - 008284
4099  - http://biorxiv.org/content/early/2014/08/23/008284.short
4100  - http://biorxiv.org/content/early/2014/08/23/008284.full
AB  - 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, c-Myc (abbreviated as OSKM) in cells expanded in lineage differentiation promoting conditions. Here we apply genetic lineage tracing for endogenous Nanog locus and X chromosome reactivation during OSKM induced trans-differentiation, as these molecular events mark final stages for acquisition of induced pluripotency. Remarkably, the majority of reprogrammed cardiomyocytes or neural stem cells derived from mouse fibroblasts via OSKM mediated trans-differentiation (∼>90%), are 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.