Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1
Open accessAbstract
The Polycomb group (PcG) gene Bmi-1 has recently been implicated in the maintenance of hematopoietic stem cells (HSC) from loss-of-function analysis. Here, we demonstrate that increased expression of Bmi-1 promotes HSC self-renewal. Forced expression of Bmi-1 enhanced symmetrical cell division of HSCs and mediated a higher probability of inheritance of stemness through cell division. Correspondingly, forced expression of Bmi-1, but not the other PcG genes, led to a striking ex vivo expansion of multipotential progenitors and marked augmentation of HSC repopulating capacity in vivo. Loss-of-function analyses revealed that among PcG genes, absence of Bmi-1 is preferentially linked with a profound defect in HSC self-renewal. Our findings define Bmi-1 as a central player in HSC self-renewal and demonstrate that Bmi-1 is a target for therapeutic manipulation of HSCs.
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Disturbing many epigenetic writers or erasers severely impairs HSC function.
“perturbation of a large number of epigenetic writers or erasers severely affects HSC function.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [65]
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- Authors
- Iwama, A., Oguro, H., Negishi, M., Kato, Y., Morita, Y., Tsukui, H., Ema, H., Kamijo, T., Katoh-Fukui, Y., Koseki, H., van Lohuizen, M., & Nakauchi, H.
- Affiliations
- Institute of Medical Science, The University of Tokyo (JP)
- Shinshu University (JP)
- National Institute for Basic Biology (JP)
- RIKEN (JP)
- Corresponding author
- Iwama, Atsushi
- Nakauchi, Hiromitsu
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2004-12
- Volume
- 21
- Issue
- 6
- Pages
- 843-851
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2050314360
- Cited by
- 515
- References
- 37
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 11 · 2022: 8 · 2021: 11 · 2020: 16 · 2019: 17 · 2018: 21 · 2017: 17 · 2016: 21 · 2015: 16 · 2014: 36 · 2013: 29 · 2012: 33
- FWCI
- 20.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- BMI1, Polycomb group genes, hematopoietic stem cells, self-renewal, symmetric cell division, multipotent progenitors, ex vivo expansion
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Hematopoietic Stem Cells, Nuclear Proteins, Proto-Oncogene Proteins, Repressor Proteins, Gene Deletion, Mice, Knockout, Cell Proliferation, Mice, Polycomb-Group Proteins, Polycomb Repressive Complex 1
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