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

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

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
Venue
The EMBO Journal
Published
2006-07-20
Volume
25
Issue
15
Pages
3515-3523
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
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
Locations
  • The EMBO Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › 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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