Hartman Institute for Therapeutic Organ Regeneration

Endothelial Jak3 expression enhances pro-hematopoietic angiocrine function in mice.

TitleEndothelial Jak3 expression enhances pro-hematopoietic angiocrine function in mice.
Publication TypeJournal Article
Year of Publication2021
AuthorsDurĂ¡n JGabriel Ba, Lu T, Houghton S, Geng F, Schreiner R, Xiang J, Rafii S, Redmond D, Lis R
JournalCommun Biol
Volume4
Issue1
Pagination406
Date Published2021 Mar 25
ISSN2399-3642
KeywordsAnimals, 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>

DOI10.1038/s42003-021-01846-3
Alternate JournalCommun Biol
PubMed ID33767339
PubMed Central IDPMC7994450
Grant ListR01 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

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Hartman Institute for Therapeutic Organ Regeneration
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