Inhibition of PRC2 enables self-renewal of blastoid-competent naive pluripotent stem cells from chimpanzee
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Naive pluripotent stem cells (PSCs) are counterparts of early epiblast in the mammalian embryo. Mouse and human naive PSCs differ in self-renewal requirements and extraembryonic lineage potency. Here, we investigated the generation of chimpanzee naive PSCs. Colonies generated by resetting or reprogramming failed to propagate. We discovered that self-renewal is enabled by inhibition of Polycomb repressive complex 2 (PRC2). Expanded cells show global transcriptome proximity to human naive PSCs and embryo pre-implantation epiblast, with shared expression of a subset of pluripotency transcription factors. Chimpanzee naive PSCs can transition to multilineage competence or can differentiate into trophectoderm and hypoblast, forming tri-lineage blastoids. They thus provide a higher primate comparative model for studying pluripotency and early embryogenesis. Genetic deletions confirm that PRC2 mediates growth arrest. Further, inhibition of PRC2 overcomes a roadblock to feeder-free propagation of human naive PSCs. Therefore, excess deposition of chromatin modification H3K27me3 is an unexpected barrier to naive PSC self-renewal.
Date Issued
2025-04-03
Date Acceptance
2025-02-04
Citation
Cell Stem Cell, 2025, 32 (4), pp.627-639.e8
ISSN
1934-5909
Publisher
Elsevier
Start Page
627
End Page
639.e8
Journal / Book Title
Cell Stem Cell
Volume
32
Issue
4
Copyright Statement
© 2025 The Author(s). Published by Elsevier Inc. 627 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40015279
PII: S1934-5909(25)00041-4
Subjects
Cell & Tissue Engineering
Cell Biology
DE-NOVO
DIFFERENTIATION
DNA METHYLATION
ESTABLISHMENT
IDENTITY
INDUCTION
LEADS
Life Sciences & Biomedicine
MONKEY
Science & Technology
SENDAI-VIRUS
TRANSCRIPTION
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2025-02-26