[Chen, Pao-Yang]TRIM28-regulated transposon repression is required for human germline competency and not primed or naïve human pluripotency

A.H&E stained images revealed that T28KO hESCs were capable of teratoma formation when transplanted into immunocompromised mice. B. Flow cytometry plot showed that T28KO hESC did not produce hPGCLC. C.Differentially expressed TEs are enriched in HERV, LTR and SVAs. D.Browser view of ATAC-seq (blue), WGBS (green) and TRIM28 ChIP-seq (yellow) at IG-DMR, the MEG3 promoter and H19. Transition from primed to naive pluripotency is associated with dynamic changes in transposable element (TE) expression and demethylation of imprinting control regions (ICRs). In mouse, ICR methylation and TE expression are each regulated by TRIM28, however, the role of TRIM28 in humans is less clear. Here, we show that a null mutation in TRIM28 causes significant alterations in TE expression in both the naïve and primed states of human pluripotency, and phenotypically this has limited effects on self-renewal, instead causing a loss of germline competency. Furthermore, we discovered that TRIM28 regulates paternal ICR methylation and chromatin accessibility in the primed state, with no effects on maternal ICRs. Taken together, our study shows that abnormal TE expression is tolerated by self-renewing human pluripotent cells, however germline competency is not. Tao Y, Yen MR, Chitiashvili1 T, Nakano H, Kim R, Hosohama L, Tan YC, Nakano1 A, Chen PY, Clark AT (2018) TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency. Stem Cell Reports. http://www.cell.com/stem-cell-reports/fulltext/S2213-6711(17)30528-3