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Publication : Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression.

First Author  Kim E Year  2017
Journal  J Exp Med Volume  214
Issue  7 Pages  1901-1912
PubMed ID  28550162 Mgi Jnum  J:244489
Mgi Id  MGI:5913268 Doi  10.1084/jem.20160719
Citation  Kim E, et al. (2017) Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression. J Exp Med 214(7):1901-1912
abstractText  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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