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Calcium/calmodulin-dependent Kinase Kinase 2 Regulates Hematopoietic Stem and Progenitor Cell Regeneration by Racioppi, Luigi; Lento, William; Huang, Wei; Arvai, Stephanie; Doan, Phuong L; Harris, Jeffrey R; Marcon, Fernando; Nakaya, Helder I; Liu, Yaping; Chao, Nelson is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Abstract Hematopoietic stem and progenitor cells (HSPCs) are predominantly quiescent in adults, but proliferate in response to bone marrow (BM) injury. Here, we show that deletion of Ca^2+^/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) promotes HSPC regeneration and hematopoietic recovery following radiation injury. Using Camkk2-enhanced green fluorescent protein (EGFP) reporter mice, we found that Camkk2 expression is developmentally regulated in HSPC. Deletion of Camkk2 in HSPC results in a significant downregulation of genes affiliated with the quiescent signature. Accordingly, HSPC from Camkk2 null mice have a high proliferative capability when stimulated __in vitro__ in the presence of BM-derived endothelial cells. In addition, __Camkk2__ null mice are more resistant to radiation injury and show accelerated hematopoietic recovery, enhanced HSPC regeneration and ultimately a prolonged survival following sublethal or lethal total body irradiation. Mechanistically, we propose that CaMKK2 regulates the HSPC response to hematopoietic damage by coupling radiation signaling to activation of the anti-proliferative AMP-activated protein kinase. Finally, we demonstrated

Who reads Calcium/calmodulin-dependent Kinase Kinase 2 Regulates Hematopoietic Stem and Progenitor Cell Regeneration?

Author

Racioppi, Luigi; Lento, William; Huang, Wei; Arvai, Stephanie; Doan, Phuong L; Harris, Jeffrey R; Marcon, Fernando; Nakaya, Helder I; Liu, Yaping; Chao, Nelson

Publisher

Nature Publishing Group; Springer Science and Business Media LLC; London: Nature Publishing Group, 2001- (ISSN 2041-4889)

Published

2017

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)