Rcor2 Is Required for Somatic Differentiation and Represses Germline Cell Fate

Lijuan Pei; Hongjie Zhang; Meihui Zhang; Yixuan Wang; Ke Wei

doi:10.1155/2022/5283615

Rcor2 Is Required for Somatic Differentiation and Represses Germline Cell Fate

Stem Cells Int. 2022 Mar 19:2022:5283615. doi: 10.1155/2022/5283615. eCollection 2022.

Authors

Lijuan Pei¹, Hongjie Zhang¹, Meihui Zhang¹, Yixuan Wang², Ke Wei¹

Affiliations

¹ Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
² Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Ministry of Education of China, Tongji University, Shanghai 200092, China.

Abstract

Rcor2, the corepressor 2 of REST, a transcriptional repressor, is predominantly expressed in embryonic stem cells (ESCs) and plays a major role in regulating ESC pluripotency and neurogenesis. The function of Rcor2 in development of other germ layers is yet unclear. We utilized a Rcor2^-/- mouse embryonic stem cell (mESC) line to investigate the role of Rcor2 in mESC differentiation. Rcor2^-/- mESC shows reduced proliferation and severely compromised capacity to differentiate to all three germ layers. In contrast, Rcor2 knockout promotes primordial germ cells (PGCs) specific gene expression and possibly PGC formation. Mechanistically, we revealed that Rcor2 inhibits expression of genes required for PGC development, such as Dppa3 and Dazl, by associating to their promoters and enhancing local suppressive H3K9me3 modifications. Our results suggest that Rcor2 plays an important role in somatic cell fate determination by suppressing PGC differentiation through regulating epigenetic modifications of PGC specific genes.