Cited by 270Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchReproductive Biology and Fertility

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Cytokine signals modulated via lipid rafts mimic niche signals and induce hibernation in hematopoietic stem cells

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Yamazaki, Satoshi, Iwama, Atsushi, Takayanagi, Shin‐ichiro, Morita, Yohei, Eto, Koji, Ema, Hideo, Nakauchi, Hiromitsu·2006·The EMBO Journal

DOI 10.1038/sj.emboj.7601236PMC PMC1538571

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Abstract

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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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: Yamazaki, Satoshi
Iwama, Atsushi
Takayanagi, Shin‐ichiro
Morita, Yohei
Eto, Koji
Ema, Hideo
Nakauchi, Hiromitsu
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2006-07-20
Volume: 25
Issue: 15
Pages: 3515-3523
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1038/sj.emboj.7601236
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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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Cytokine signals modulated via lipid rafts mimic niche signals and induce hibernation in hematopoietic stem cells

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