Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice
Open accessAbstract
The Polycomb group (PcG) gene Bmi1 promotes cell proliferation and stem cell self-renewal by repressing the Ink4a/Arf locus. We used a genetic approach to investigate whether Ink4a or Arf is more critical for relaying Bmi1 function in lymphoid cells, neural progenitors, and neural stem cells. We show that Arf is a general target of Bmi1, however particularly in neural stem cells, derepression of Ink4a contributes to Bmi1-/- phenotypes. Additionally, we demonstrate haploinsufficient effects for the Ink4a/Arf locus downstream of Bmi1 in vivo. This suggests differential, cell type-specific roles for Ink4a versus Arf in PcG-mediated (stem) cell cycle control.
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Several studies have established a role for Bmi1 in the regulation of p16Ink4a.
“Because several studies have established a role for the polycomb group protein Bmi1 in the regulation of p16Ink4a (26–28), we analyzed the levels of Bmi1.”
From Age-Dependent Decline in β-Cell Proliferation Restricts the Capacity of β-Cell Regeneration in Mice (2009) · cites this paper as [26]
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- Authors
- Bruggeman, S. W. M., Valk-Lingbeek, M. E., van der Stoop, P. P. M., Jacobs, J. J. L., Kieboom, K., Tanger, E., Hulsman, D., Leung, C., Arsenijevic, Y., Marino, S., & van Lohuizen, M.
- Affiliations
- University of Zurich (CH)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-06-15
- Volume
- 19
- Issue
- 12
- Pages
- 1438-1443
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1151660
- OpenAlex
- W2168571184
- Cited by
- 315
- References
- 38
- Citations by year
- 2026: 4 · 2024: 5 · 2023: 2 · 2022: 9 · 2021: 10 · 2020: 8 · 2019: 10 · 2018: 11 · 2017: 7 · 2016: 10 · 2015: 18 · 2014: 19 · 2013: 20 · 2012: 18
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Oncosuisse
- KWF Kankerbestrijding
- Universität Zürich
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- INK4A, ARF, BMI1, Polycomb group genes, neural stem cell self-renewal, cell proliferation, INK4a/ARF locus, haploinsufficiency, lymphoid cells, neural progenitor cells, cell cycle reprogramming
- MeSH terms
- Animals, Cell Differentiation, Cerebellum, Heterozygote, Lymphoid Tissue, Mice, Inbred C57BL, Neurons, Nuclear Proteins, Proto-Oncogene Proteins, Repressor Proteins, RNA, Messenger, Cellular Senescence, Mice, Knockout, Cyclin-Dependent Kinase Inhibitor p16, Genes, p16, Tumor Suppressor Protein p14ARF, Multipotent Stem Cells, Cell Proliferation, Mice, Polycomb Repressive Complex 1
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