Apobec2 plays a critical role in self-renewal of mouse ESCs and reprogramming of mouse iPSCs

Abstract

Apolipoprotein B mRNA-editing enzyme catalytic subunit 2 (APOBEC2) is known that highly expressed in heart and muscle tissues and plays an important role in regulating and maintaining muscle development in mammals. Besides regulation of muscle development, Apobec2 expression and function in other cells and tissues are still unknown – especially in pluripotent stem cells.

Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the pre-implantation blastocyst. ESCs can be propagated stably in an undifferentiated state in vitro (self-renewal) and, under the appropriate culture conditions, can be induced to differentiate into a variety of cell types (pluripotency).

Proper telomere length is essential for self-renewal and pluripotency of ESCs. Also, telomerase plays a critical role in reprogramming and self-renewal of induced pluripotent stem cells (iPSCs). However, the mechanisms of telomere length regulation during induction and proliferation of iPSCs remain elusive. Here, we reports that Apobec2 is specifically expressed in mouse ESCs and iPSCs, and regulates self-renewal of mouse ESCs as well as reprogramming of mouse iPSCs by regulating expression of Tert mRNA.

Knock down of Apobec2 reduced colonization and proliferation of mouse ESCs. Furthermore, sphere-forming assay showed decreased self-renewal of mouse ESCs by Apobec2 knock down. During reprogramming of mouse iPSCs, the expression level of Apobec2 mRNA was increased in time dependent manner. Next, we performed knock down and overexpression of Apobec2 in prior to mouse iPSC reprogramming, and found that Apobec2 positively regulated reprogramming of mouse iPSCs. In this study, our results suggest that Apobec2 plays an important role in modulating self-renewal of mouse ESCs as well as iPSC reprogramming.