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

ABSTRACT: 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.

SUBMITTER: Kim E

PROVIDER: S-EPMC5502420 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Kim Eunsun E Cheng Ying Y Bolton-Gillespie Elisabeth E Cai Xiongwei X Ma Connie C Tarangelo Amy A Le Linh L Jambhekar Madhumita M Raman Pichai P Hayer Katharina E KE Wertheim Gerald G Speck Nancy A NA Tong Wei W Viatour Patrick P

The Journal of experimental medicine 20170526 7

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 <i>Socs3</i>, a potent inhibitor of Jak2 signaling, in cycling HSCs. Aberrant activation ...[more]

PMID: 28550162

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