Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression.
Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression.
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DOI：
10.1084/jem.20160719
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发表时间：
2017-07-03
期刊：
影响因子：
--
通讯作者：
Viatour P
中科院分区：
文献类型：
--
作者：
Kim E;Cheng Y;Bolton-Gillespie E;Cai X;Ma C;Tarangelo A;Le L;Jambhekar M;Raman P;Hayer KE;Wertheim G;Speck NA;Tong W;Viatour P
调控HSC稳态的机制仍然知之甚少。在这里，Kim等人将Rb/E2 f模块鉴定为HSC中细胞周期和稳态调节的中心分子枢纽。这种机制驱动增殖的HSC的强制分化，以避免它们不必要的积累。造血干细胞（HSC）长时间退出静止状态会通过一种未知的机制逐渐损害其在骨髓中的稳态。我们发现，Rb蛋白，这是主要的执法人员的静止，维持HSC的稳态，通过积极调节血小板生成素（Tpo）介导的Jak 2信号。Rb家族蛋白失活触发了循环HSC中E2 f介导的Socs 3（Jak 2信号传导的有效抑制剂）的进行性反式激活。Socs 3的异常激活损害Tpo信号传导并导致HSC稳态受损。因此，Rb蛋白通过协调HSC中细胞周期和Jak 2信号传导的调节而充当静止和稳态的中心枢纽。
The mechanisms regulating the homeostasis of HSCs remain poorly understood. Here, Kim et al. identify the Rb/E2f module as a central molecular hub in the regulation of cell cycle and homeostasis in HSCs. This mechanism drives the enforced differentiation of proliferative HSCs to avoid their unnecessary accumulation. Prolonged exit from quiescence by hematopoietic stem cells (HSCs) progressively impairs their homeostasis in the bone marrow through an unidentified mechanism. We show that Rb proteins, which are major enforcers of quiescence, maintain HSC homeostasis by positively regulating thrombopoietin (Tpo)-mediated Jak2 signaling. Rb family protein inactivation triggers the progressive E2f-mediated transactivation of Socs3, a potent inhibitor of Jak2 signaling, in cycling HSCs. Aberrant activation of Socs3 impairs Tpo signaling and leads to impaired HSC homeostasis. Therefore, Rb proteins act as a central hub of quiescence and homeostasis by coordinating the regulation of both cell cycle and Jak2 signaling in HSCs.
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影响因子：
20.3
作者：
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DOI：
10.1073/pnas.95.3.1195
发表时间：
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