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Updated: Sep 8, 2025
08:21
In Vitro Differentiation of Human Pluripotent Stem Cells into Trophoblastic Cells
Published on: March 16, 2017
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Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction
Dick W Zijlmans1, Irene Talon2, Sigrid Verhelst3
1Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Oncode Institute, Radboud University Nijmegen, Nijmegen, The Netherlands.
Nature Cell Biology
|June 13, 2022
Summary
Human naive pluripotent stem cells possess chromatin barriers, contrary to previous assumptions. Polycomb repressive complex 2 (PRC2) restricts trophoblast differentiation, revealing epigenetic restrictions in these cells.
Area of Science:
- Stem cell biology
- Epigenetics
- Developmental biology
Background:
- Human naive pluripotent stem cells are believed to have unrestricted lineage potential due to a lack of chromatin-based barriers.
- This assumption, however, has not been experimentally verified, leaving a gap in understanding their epigenetic regulation.
Purpose of the Study:
- To investigate the chromatin landscape and epigenetic state of human naive and primed pluripotent stem cells.
- To determine if chromatin-based lineage barriers exist in naive pluripotent stem cells and identify the underlying molecular mechanisms.
Main Methods:
- Comparative analysis of the chromatin-associated proteome, histone modifications (including H3K27me3), and transcriptomes between naive and primed human pluripotent stem cells.
- Functional assays involving Polycomb repressive complex 2 (PRC2) inhibition to assess its role in lineage restriction.
- Analysis of human blastoids to evaluate the impact of PRC2 activity on trophoblast differentiation and development.
Main Results:
- Integrated analysis revealed significant differences in chromatin modules between naive and primed stem cells.
- A notable enrichment of Polycomb repressive complex 2 (PRC2)-associated H3K27me3 was identified in naive pluripotent stem cells, particularly at promoters of lineage-determining genes.
- PRC2 activity was confirmed as a chromatin barrier restricting trophoblast lineage differentiation; its inhibition promoted trophoblast fate and blastoid cavity formation.
Conclusions:
- Human naive pluripotent stem cells are not epigenetically unrestricted as previously thought.
- Chromatin mechanisms, specifically PRC2-mediated H3K27 trimethylation, actively oppose the induction of alternative cell fates, such as trophoblast differentiation.
- These findings redefine the epigenetic landscape of naive pluripotency and have implications for stem cell differentiation protocols and developmental studies.
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