Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation
Abstract
The balance between self-renewal and differentiation of adult stem cells is essential for tissue homeostasis. Here we show that in the haematopoietic system this process is governed by polycomb chromobox (Cbx) proteins. Cbx7 is specifically expressed in haematopoietic stem cells (HSCs), and its overexpression enhances self-renewal and induces leukaemia. This effect is dependent on integration into polycomb repressive complex-1 (PRC1) and requires H3K27me3 binding. In contrast, overexpression of Cbx2, Cbx4 or Cbx8 results in differentiation and exhaustion of HSCs. ChIP-sequencing analysis shows that Cbx7 and Cbx8 share most of their targets; we identified approximately 200 differential targets. Whereas genes targeted by Cbx8 are highly expressed in HSCs and become repressed in progenitors, Cbx7 targets show the opposite expression pattern. Thus, Cbx7 preserves HSC self-renewal by repressing progenitor-specific genes. Taken together, the presence of distinct Cbx proteins confers target selectivity to PRC1 and provides a molecular balance between self-renewal and differentiation of HSCs.
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In mice, altered expression of wild-type or mutant epigenetic writers affects HSC self-renewal.
“studies in mice have revealed that (enforced) altered expression of wild-type or mutant epigenetic writers affects self-renewal of HSCs.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [68]
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References 60 · Cited by 237
- Authors
- Klauke, K., Radulović, V., Broekhuis, M., Weersing, E., Zwart, E., Olthof, S., Ritsema, M., Bruggeman, S., Wu, X., Helin, K., Bystrykh, L., & de Haan, G.
- Affiliations
- University Medical Center Groningen (NL)
- University of Copenhagen (DK)
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2013-03-17
- Volume
- 15
- Issue
- 4
- Pages
- 353-362
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2120121380
- Cited by
- 237
- References
- 60
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 10 · 2023: 10 · 2022: 23 · 2021: 17 · 2020: 28 · 2019: 24 · 2018: 16 · 2017: 23 · 2016: 27 · 2015: 10 · 2014: 22 · 2013: 6
- FWCI
- 15.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Ministry of Earth Sciences
- Ministry of Education, India
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- Polycomb group proteins, CBX7, CBX8, CBX2, CBX4, hematopoietic stem cells, self-renewal, differentiation, PRC1, H3K27me3, chromatin repression, leukemia, progenitor cells
- MeSH terms
- Animals, Cell Differentiation, Flow Cytometry, Hematopoietic Stem Cells, Leukemia, Experimental, Ligases, Mice, Inbred C57BL, Mice, Inbred DBA, RNA, Messenger, Blotting, Western, Survival Rate, Apoptosis, Reverse Transcriptase Polymerase Chain Reaction, Mitochondrial Membrane Transport Proteins, RNA, Small Interfering, Ubiquitin-Protein Ligases, Chromatin Immunoprecipitation, Cell Proliferation, Mice, Real-Time Polymerase Chain Reaction, Polycomb-Group Proteins, Polycomb Repressive Complex 1
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