Title | Endothelial Jak3 expression enhances pro-hematopoietic angiocrine function in mice. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | DurĂ¡n JGabriel Ba, Lu T, Houghton S, Geng F, Schreiner R, Xiang J, Rafii S, Redmond D, Lis R |
Journal | Commun Biol |
Volume | 4 |
Issue | 1 |
Pagination | 406 |
Date Published | 2021 Mar 25 |
ISSN | 2399-3642 |
Keywords | Animals, Endothelial Cells, Female, Gene Knock-In Techniques, Hematopoiesis, Hematopoietic Stem Cells, Janus Kinase 3, Male, Mice |
Abstract | <p>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.</p> |
DOI | 10.1038/s42003-021-01846-3 |
Alternate Journal | Commun Biol |
PubMed ID | 33767339 |
PubMed Central ID | PMC7994450 |
Grant List | R01 HL115128 / HL / NHLBI NIH HHS / United States R35 HL150809 / HL / NHLBI NIH HHS / United States RC2 DK114777 / DK / NIDDK NIH HHS / United States R01 HL139056 / HL / NHLBI NIH HHS / United States R01 HL119872 / HL / NHLBI NIH HHS / United States U01 AI138329 / AI / NIAID NIH HHS / United States R01 HL128158 / HL / NHLBI NIH HHS / United States R01 DK095039 / DK / NIDDK NIH HHS / United States |