Open AccessThe pluripotent stem cell-specific transcript ESRG is dispensable for human pluripotency
Author(s) -
Kazutoshi Takahashi,
Michiko Nakamura,
Chikako Okubo,
Zane Kliesmete,
Mari Ohnuki,
Megumi Narita,
Akira Watanabe,
Mai Ueda,
Yasuhiro Takashima,
Ines Hellmann,
Shinya Yamanaka
Publication year - 2021
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1009587
Subject(s) - biology , induced pluripotent stem cell , sox2 , klf4 , crispr , transcriptome , embryonic stem cell , microbiology and biotechnology , cellular differentiation , genetics , gene , hek 293 cells , gene expression , regulation of gene expression , stem cell
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.