Endothelial Jak3 expression enhances pro-hematopoietic angiocrine function in mice

Commun Biol. 2021 Mar 25;4(1):406. doi: 10.1038/s42003-021-01846-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endothelial Cells / metabolism*
  • Female
  • Gene Knock-In Techniques
  • Hematopoiesis / genetics*
  • Hematopoietic Stem Cells / metabolism*
  • Janus Kinase 3 / genetics*
  • Janus Kinase 3 / metabolism
  • Male
  • Mice

Substances

  • Jak3 protein, mouse
  • Janus Kinase 3