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bioRxiv · 10.1101/008284

Frequent and Transient Acquisition of Pluripotency During Somatic Cell Trans-differentiation with iPSC Reprogramming Factors

Itay Maza·Inbal Casoi·Sergey Viukov·Yoach Rais·Asaf Zviran·Shay Geula·Vladislav Krupalnik·Mirie Zerbib·Rada Massarwa·Noa Novershtern·Jacob Hanna
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Abstract

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.

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Itay Maza, Inbal Casoi, Sergey Viukov, Yoach Rais, Asaf Zviran, Shay Geula, Vladislav Krupalnik, Mirie Zerbib, Rada Massarwa, Noa Novershtern, Jacob Hanna. 2014-08-23. Frequent and Transient Acquisition of Pluripotency During Somatic Cell Trans-differentiation with iPSC Reprogramming Factors. https://doi.org/10.1101/008284

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