2006年8月
Cytokine signals modulated via lipid rafts mimic niche signals and induce hibernation in hematopoietic stem cells
EMBO JOURNAL
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- 巻
- 25
- 号
- 15
- 開始ページ
- 3515
- 終了ページ
- 3523
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/sj.emboj.7601236
- 出版者・発行元
- NATURE PUBLISHING GROUP
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.
- リンク情報
- ID情報
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- DOI : 10.1038/sj.emboj.7601236
- ISSN : 0261-4189
- Web of Science ID : WOS:000239626000008