Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner.
Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner.
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DOI：
10.1038/s41467-023-41691-y
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发表时间：
2023-09-28
影响因子：
16.6
通讯作者：
Jacobsen, Sten Eirik W.
中科院分区：
文献类型：
--
作者：
Luis, Tiago C.;Barkas, Nikolaos;Carrelha, Joana;Giustacchini, Alice;Mazzi, Stefania;Norfo, Ruggiero;Wu, Bishan;Aliouat, Affaf;Guerrero, Jose A.;Rodriguez-Meira, Alba;Bouriez-Jones, Tiphaine;Macaulay, Iain C.;Jasztal, Maria;Zhu, Guangheng;Ni, Heyu;Robson, Matthew J.;Blakely, Randy D.;Mead, Adam J.;Nerlov, Claus;Ghevaert, Cedric;Jacobsen, Sten Eirik W.
造血干细胞（HSC）驻留在骨髓中的专门小生境中，负责多种短寿命血细胞谱系在稳态和响应不同挑战时的平衡输出。然而，HSC通过其小生境感知特定血细胞谱系急性丧失的反馈机制仍有待建立。虽然所有的HSC都能补充血小板，但以前的研究表明，大部分HSC在分子上被诱导为巨核细胞-血小板谱系，并在血小板耗竭时迅速招募增殖。血小板以活化依赖性方式正常周转，本文通过诱导血小板活化和消耗的抗体模拟。抗体介导的血小板活化上调血小板和骨髓细胞外液中白细胞介素-1（IL-1）的表达。遗传实验表明，不是IL-1直接激活HSC，而是表达IL-1受体的骨髓Lepr+血管周围小生境细胞的激活对于血小板激活和消耗后静止HSC的最佳激活至关重要。这些发现确定了一种反馈机制，通过该机制，激活诱导的成熟血细胞谱系的消耗导致HSC的小生境依赖性激活以恢复其稳态。造血干细胞（HSC）补充血细胞。在这里，路易斯等人，鉴定由活化的血小板分泌的IL-1通过小生境Lepr+细胞发出信号以活化HSC并恢复血小板稳态的反馈机制。
Hematopoietic stem cells (HSCs) residing in specialized niches in the bone marrow are responsible for the balanced output of multiple short-lived blood cell lineages in steady-state and in response to different challenges. However, feedback mechanisms by which HSCs, through their niches, sense acute losses of specific blood cell lineages remain to be established. While all HSCs replenish platelets, previous studies have shown that a large fraction of HSCs are molecularly primed for the megakaryocyte-platelet lineage and are rapidly recruited into proliferation upon platelet depletion. Platelets normally turnover in an activation-dependent manner, herein mimicked by antibodies inducing platelet activation and depletion. Antibody-mediated platelet activation upregulates expression of Interleukin-1 (IL-1) in platelets, and in bone marrow extracellular fluid in vivo. Genetic experiments demonstrate that rather than IL-1 directly activating HSCs, activation of bone marrow Lepr+ perivascular niche cells expressing IL-1 receptor is critical for the optimal activation of quiescent HSCs upon platelet activation and depletion. These findings identify a feedback mechanism by which activation-induced depletion of a mature blood cell lineage leads to a niche-dependent activation of HSCs to reinstate its homeostasis. Hematopoietic stem cells (HSCs) replenish blood cells. Here, Luis et al., identify a feedback mechanism by which IL-1 secreted by activated platelets signals through niche Lepr+ cells to activate HSCs and restore platelet homeostasis.
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影响因子：
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作者：
Herd, Oliver J.;Rani, Gulab Fatima;Hewitson, James P.;Hogg, Karen;Stone, Andrew P.;Cooper, Nichola;Kent, David G.;Genever, Paul G.;Hitchcock, Ian S.
通讯作者：
Hitchcock, Ian S.
影响因子：
7.4
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