Cited by 1,871Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchBlood disorders and treatments

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Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.

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Park, In-kyung, Qian, Dalong, Kiel, Mark, Becker, Michael W., Pihalja, Michael, Weissman, Irving L., Morrison, Sean J., Clarke, Michael F.·2003·Nature

DOI 10.1038/nature01587

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Abstract

A central issue in stem cell biology is to understand the mechanisms that regulate the self-renewal of haematopoietic stem cells (HSCs), which are required for haematopoiesis to persist for the lifetime of the animal. We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. The number of HSCs in the fetal liver of Bmi-1-/- mice was normal. In postnatal Bmi-1-/- mice, the number of HSCs was markedly reduced. Transplanted fetal liver and bone marrow cells obtained from Bmi-1-/- mice were able to contribute only transiently to haematopoiesis. There was no detectable self-renewal of adult HSCs, indicating a cell autonomous defect in Bmi-1-/- mice. A gene expression analysis revealed that the expression of stem cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice. Expression of p16Ink4a and p19Arf in normal HSCs resulted in proliferative arrest and p53-dependent cell death, respectively. Our results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs.

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Authors: Park, I.-K., Qian, D., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., & Clarke, M. F.
Affiliations: University of Michigan (US)
Howard Hughes Medical Institute (US)
Stanford Medicine (US)
Corresponding author: Clarke, Michael F.
ORCID: Park, In-kyung
Qian, Dalong
Kiel, Mark
Becker, Michael W.
Weissman, Irving L.
Morrison, Sean J.
Clarke, Michael F.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2003-04-20
Volume: 423
Issue: 6937
Pages: 302-305
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature01587
OpenAlex: W2021050536
Cited by: 1,871
References: 31
Citations by year: 2026: 16 · 2025: 19 · 2024: 15 · 2023: 29 · 2022: 50 · 2021: 48 · 2020: 45 · 2019: 51 · 2018: 52 · 2017: 68 · 2016: 79 · 2015: 81 · 2014: 97 · 2013: 100 · 2012: 127
FWCI: 55.81
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Deep Blue (University of Michigan) (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: University of Michigan
National Institutes of Health
Topics: Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Health Sciences › Medicine › Hematology › Blood disorders and treatments
Keywords: BMI1, hematopoietic stem cells, self-renewal, stem cell maintenance, p16INK4a, p19ARF, p53-dependent cell death, growth arrest, cell survival genes, hematopoiesis, bone marrow
MeSH terms: Proto-Oncogene Mas, Animals, Bone Marrow Cells, Cell Division, Gene Expression Regulation, Hematopoietic Stem Cells, Humans, Liver, Models, Biological, Nuclear Proteins, Proto-Oncogene Proteins, Repressor Proteins, RNA, Messenger, Bone Marrow Transplantation, Gene Deletion, Hematopoietic Stem Cell Transplantation, Cyclin-Dependent Kinase Inhibitor p16, Tumor Suppressor Protein p14ARF, Mice, Polycomb Repressive Complex 1

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Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.

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