RT Journal Article SR Electronic T1 The pluripotent stem cell-specific transcript ESRG is dispensable for human pluripotency JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.25.397935 DO 10.1101/2020.11.25.397935 A1 Kazutoshi Takahashi A1 Michiko Nakamura A1 Megumi Narita A1 Akira Watanabe A1 Mai Ueda A1 Yasuhiro Takashima A1 Shinya Yamanaka YR 2020 UL http://biorxiv.org/content/early/2020/11/27/2020.11.25.397935.abstract AB Human pluripotent stem cells (PSCs) express human endogenous retrovirus type-H (HERV-H), which exists as more than a thousand copies on the human genome and frequently produces chimeric transcripts as long-non-coding RNAs (lncRNAs) fused with downstream neighbor genes. Previous studies showed that HERV-H expression is required for the maintenance of PSC identity, and aberrant HERV-H expression attenuates neural differentiation potentials, however, little is known about the actual of function of HERV-H. In this study, we focused on ESRG, which is known as a PSC-related HERV-H-driven lncRNA. The global transcriptome data of various tissues and cell lines and quantitative expression analysis of PSCs showed that ESRG expression is much higher than other HERV-Hs and tightly silenced after differentiation. However, the loss of function by the complete excision of the entire ESRG gene body using a CRISPR/Cas9 platform revealed that ESRG is dispensable for the maintenance of the primed and naïve pluripotent states. The loss of ESRG hardly affected the global gene expression of PSCs or the differentiation potential toward trilineage. Differentiated cells derived from ESRG-deficient PSCs retained the potential to be reprogrammed into induced PSCs (iPSCs) by the forced expression of OCT3/4, SOX2, and KLF4. In conclusion, ESRG is dispensable for the maintenance and recapturing of human pluripotency.Competing Interest StatementK.T. is on the scientific advisory board of I Peace, Inc. without salary. S.Y. is a scientific advisor (without salary) of iPS Academia Japan. All other authors have no conflict of interest.