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Cytokine signals modulated via lipid rafts mimic niche signals and induce hibernation in hematopoietic stem cells
Open accessAbstract
Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) niche in a noncycling state and enter the cell cycle at long intervals. However, little is known about inter- and intracellular signaling mechanisms underlying this unique property of HSCs. Here, we show that lipid raft clustering is a key event in the regulation of HSC dormancy. Freshly isolated HSCs from the BM niche lack lipid raft clustering, exhibit repression of the AKT-FOXO signaling pathway, and express abundant p57(Kip2) cyclin-dependent kinase inhibitor. Lipid raft clustering induced by cytokines is essential for HSC re-entry into the cell cycle. Conversely, inhibition of lipid raft clustering caused sustained nuclear accumulation of FOXO transcription factors and induced HSC hibernation ex vivo. These data establish a critical role for lipid rafts in regulating the cell cycle, the survival, and the entry into apoptosis of HSCs and uncover a striking similarity in HSC hibernation and Caenorhabditis elegans dauer formation.
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“low levels of p57 have been associated with stem cell hibernation (Yamazaki et al., 2006)”
From Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells (2017) · cites this paper as Yamazaki et al., 2006
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Metadata
- Authors
- Yamazaki, S., Iwama, A., Takayanagi, S., Morita, Y., Eto, K., Ema, H., & Nakauchi, H.
- Affiliations
- Institute of Medical Science, The University of Tokyo (JP)
- Chiba University (JP)
- Corresponding author
- Nakauchi, Hiromitsu
- ORCID
- Venue
- The EMBO Journal
- Published
- 2006-07-20
- Volume
- 25
- Issue
- 15
- Pages
- 3515-3523
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1538571
- OpenAlex
- W2125723206
- Cited by
- 270
- References
- 33
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 11 · 2021: 9 · 2020: 7 · 2019: 7 · 2018: 4 · 2017: 9 · 2016: 18 · 2015: 14 · 2014: 17 · 2013: 22 · 2012: 17
- FWCI
- 12.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Reproductive Medicine › Reproductive Biology and Fertility
- Keywords
- hematopoietic stem cells, lipid rafts, cell cycle re-entry, p57KIP2, cytokine signaling, bone marrow microenvironment, apoptosis, dauer formation, Caenorhabditis elegans
- MeSH terms
- Animals, Cell Cycle, Cells, Cultured, Fluorescent Antibody Technique, Hematopoietic Stem Cells, Mice, Inbred C57BL, Stem Cells, Signal Transduction, Cytokines, Caenorhabditis elegans, Apoptosis, Membrane Microdomains, Mice
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