期刊
COMMUNICATIONS BIOLOGY
卷 4, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s42003-021-01846-3
关键词
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资金
- Ansary Stem Cell Institute at Weill Cornell Medicine
- Tri-Institutional Stem Cell Initiative [TRI-SCI 2013-032, 2014-023, 2016-013, 2019029]
- National Institutes of Health (NIH) [R35 HL150809, R01 DK095039, R01 HL119872, R01 HL128158, R01 HL115128, R01 HL139056, RC2 DK114777, U01AI138329]
- New York State Stem Cell Science (NYSTEM) [C026878, C028117, C029156, C030160]
- Weill Cornell Medicine Daedalus Fund for Innovation
- Empire State Stem Cell Board
- Qatar National Priorities Research Program [NPRP 8-1898-3-392]
Jak3, a member of the Jak family of secondary messengers, is expressed in various endothelial cell types, with high expression in the bone marrow; Jak3 in the bone marrow niche plays a crucial role in maintaining long-term repopulating hematopoietic stem cells; Overexpression of Jak3 in endothelial cells enhances the potential for expanding LT-HSCs.
Jak3 is the only non-promiscuous member of the Jak family of secondary messengers. Studies to date have focused on understanding and targeting the cell-autonomous role of Jak3 in immunity, while functional Jak3 expression outside the hematopoietic system remains largely unreported. We show that Jak3 is expressed in endothelial cells across hematopoietic and non-hematopoietic organs, with heightened expression in the bone marrow. The bone marrow niche is understood as a network of different cell types that regulate hematopoietic function. We show that the Jak3(-/-) bone marrow niche is deleterious for the maintenance of long-term repopulating hematopoietic stem cells (LT-HSCs) and that JAK3-overexpressing endothelial cells have increased potential to expand LT-HSCs in vitro. This work may serve to identify a novel function for a highly specific tyrosine kinase in the bone marrow vascular niche and to further characterize the LT-HSC function of sinusoidal endothelium. Barcia Duran et al. show that the tyrosine kinase gene Jak3 is expressed in multiple endothelial cell types in the mouse, including in non-hematopoietic organs, with particularly high expression in the bone marrow. Using mice lacking Jak3, they show that Jak3 expressed in the bone marrow niche is important for maintaining long-term repopulating hematopoietic stem cells.
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