NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE232076 Query DataSets for GSE232076
Status Public on Apr 24, 2024
Title In vitro reconstitution of epigenetic reprogramming in the human germ line [RNA-Seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Epigenetic reprogramming resets parental epigenetic memories and differentiates primordial germ cells (PGCs) into mitotic pro-spermatogonia or oogonia, ensuring sexually dimorphic germ-cell development for totipotency. However, the mechanism of epigenetic reprogramming in humans remains unknown. Here, we establish a robust strategy for inducing epigenetic reprogramming and differentiation of pluripotent stem cell (PSC)-derived human PGC-like cells (hPGCLCs) into mitotic pro-spermatogonia or oogonia, coupled with their extensive amplification (~>10(10)-fold). Strikingly, bone morphogenetic protein (BMP) signaling is the key driver of these processes. Mechanistically, BMP signaling attenuates the mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK) pathway and both de novo and maintenance DNA methyltransferase (DNMT) activities, promoting replication-coupled, passive DNA demethylation. On the other hand, tens-eleven translocation (TET) 1, an active DNA demethylase abundant in human germ cells, plays a dual role in hPGCLC differentiation: safeguarding hPGCLCs against differentiation into amnion-like cells by repressing key genes with bivalent promoters, and facilitating coordinated activation of genes vital for spermatogenesis and oogenesis by demethylating their promoters. Our study uncovers the principle of epigenetic reprogramming in humans, making a fundamental advance in human biology, and through the generation of abundant mitotic pro-spermatogonia and oogonia-like cells, represents a milestone for human in vitro gametogenesis (IVG) research and its potential translation into reproductive medicine.
 
Overall design Transcriptome analysis of human PGCLCs expanded with BMP signaling.
 
Contributor(s) Murase Y, Yokogawa R, Yabuta Y, Nagano M, Katou Y, Mizuyama M, Kitamura A, Puangsricharoen P, Yamashiro C, Hu B, Mizuta K, Tsujimura T, Yamamoto T, Ogata K, Ishihama Y, Saitou M
Citation(s) 38768632
Submission date May 09, 2023
Last update date Jul 24, 2024
Contact name Yukihiro Yabuta
E-mail(s) yabyab@anat2.med.kyoto-u.ac.jp
Organization name Kyoto University, Graduate school of medicine
Department Anatomy and Cell Biology
Street address Yoshida-Konoe-cho, Sakyo-ku
City Kyoto
State/province Kyoto
ZIP/Postal code 606-8501
Country Japan
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (89)
GSM7311485 F1-AGVT_iPSC (MS356_047)
GSM7311486 F1-AGVT_hPGCLC,rep1 (MS356_048)
GSM7311487 F1-AGVT_hPGCLC,rep2 (MS356_059)
This SubSeries is part of SuperSeries:
GSE232078 In vitro reconstitution of epigenetic reprogramming in the human germ line
Relations
BioProject PRJNA970757

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE232076_RAW.tar 112.3 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap