Cited by 515Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchPluripotent Stem Cells Research

Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1

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Iwama, Atsushi, Oguro, Hideyuki, Negishi, Masamitsu, Kato, Yuko, Morita, Youhei, Tsukui, Hiroko, Ema, Hideo, Kamijo, Takehiko +4 more·2004·Immunity

Abstract

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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Crossref · 10.1016/j.immuni.2004.11.004

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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
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
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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