Rheb1 loss leads to increased hematopoietic stem cell proliferation and myeloid-biased differentiation in vivo.

Rheb1 loss leads to increased hematopoietic stem cell proliferation and myeloid-biased differentiation in vivo. Haematologica. 2018 Sep 27;: Authors: Wang X, Gao Y, Gao J, Li M, Zhou M, Wang J, Pang Y, Cheng H, Yuan C, Chu Y, Jiang Y, Zhou J, Luo HR, Ju Z, Cheng T, Yuan W Abstract Hematopoietic stem cells constitute a unique subpopulation of blood cells that have the ability to give rise to all types of mature cells in response to physiological demands. However, the intrinsic molecular machinery that regulates this transformative property remains elusive. In this paper, we demonstrate that small GTPase Rheb1 is a critical regulator of proliferation and differentiation of hematopoietic stem cells in vivo. Rheb1 deletion led to increased phenotypic hematopoietic stem cells/hematopoietic progenitor cells proliferation under the steady state condition. Over-proliferating Rheb1-deficient hematopoietic stem cells were severely impaired in functional repopulation assays, and they failed to regenerate blood system when challenged with hematopoietic ablation by sublethal irradiation. Additionally, it was discovered that Rheb1 loss caused neutrophil immaturation by reducing mTORC1 activity, and that activation of the mTORC1 signaling pathway by mTOR activator 3BDO partially restored the maturation of Rheb1-deficient neutrophils. Rheb1 deficiency led to a progressive enlargement of hematopoietic stem cells population and eventual excessive myel...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research