THE ROLE OF OOCYTE-ENRICHED TCL1 FAMILY IN IPSC REPROGRAMMING

Abstract

Reprogramming via somatic cell nuclear reprogramming (SCNT) is rapid and efficient, and the resultant reprogrammed pluripotent stem cells are uniformly bona fide pluripotent cells. On the contrary, transcription factor mediated direct reprogramming is inefficient, slow, and rarely yields authentic pluripotent stem cells. Here, I demonstrate that the overexpression of oocyte-expressed TCL1 family member genes (TCL1 and TCL1b1) enhanced the efficiency and kinetics of iPSC reprogramming and also the quality of the resultant iPSCs. TCL1 and TCL1b1 are known to bind to and potentiate the activity of the AKT1 signaling kinase, and accordingly, overexpression of AKT1 also enhanced iPSC cell reprogramming efficiency. In addition, PNPase is another newly identified binding partner of TCL1 and was shown in the present study to be a downstream AKT1-independent target of TCL1. PnPase is an interesting target to study with the hope that downregulation of PNPase would enhance the metabolic and nuclear reprogramming.