TGF-β as a candidate bone marrow niche signal to induce hematopoietic stem cell hibernation
S Yamazaki, A Iwama, S Takayanagi… - Blood, The Journal …, 2009 - ashpublications.org
S Yamazaki, A Iwama, S Takayanagi, K Eto, H Ema, H Nakauchi
Blood, The Journal of the American Society of Hematology, 2009•ashpublications.orgHematopoietic stem cells (HSCs) reside in a bone marrow niche in a nondividing state from
which they occasionally are aroused to undergo cell division. Yet, the mechanism
underlying this unique feature remains largely unknown. We have recently shown that
freshly isolated CD34− KSL hematopoietic stem cells (HSCs) in a hibernation state exhibit
inhibited lipid raft clustering. Lipid raft clustering induced by cytokines is essential for HSCs
to augment cytokine signals to the level enough to re-enter the cell cycle. Here we screened …
which they occasionally are aroused to undergo cell division. Yet, the mechanism
underlying this unique feature remains largely unknown. We have recently shown that
freshly isolated CD34− KSL hematopoietic stem cells (HSCs) in a hibernation state exhibit
inhibited lipid raft clustering. Lipid raft clustering induced by cytokines is essential for HSCs
to augment cytokine signals to the level enough to re-enter the cell cycle. Here we screened …
Abstract
Hematopoietic stem cells (HSCs) reside in a bone marrow niche in a nondividing state from which they occasionally are aroused to undergo cell division. Yet, the mechanism underlying this unique feature remains largely unknown. We have recently shown that freshly isolated CD34−KSL hematopoietic stem cells (HSCs) in a hibernation state exhibit inhibited lipid raft clustering. Lipid raft clustering induced by cytokines is essential for HSCs to augment cytokine signals to the level enough to re-enter the cell cycle. Here we screened candidate niche signals that inhibit lipid raft clustering, and identified that transforming growth factor-β (TGF-β) efficiently inhibits cytokine-mediated lipid raft clustering and induces HSC hibernation ex vivo. Smad2 and Smad3, the signaling molecules directly downstream from and activated by TGF-β receptors were specifically activated in CD34−KSL HSCs in a hibernation state, but not in cycling CD34+KSL progenitors. These data uncover a critical role for TGF-β as a candidate niche signal in the control of HSC hibernation and provide TGF-β as a novel tool for ex vivo modeling of the HSC niche.
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