Ansary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.
Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and Infertility, Weill Cornell Medicine, New York, NY, 10065, USA.
Commun Biol. 2021 Mar 25;4(1):406. doi: 10.1038/s42003-021-01846-3.
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.
Jak3 是 Jak 家族中唯一的非多功能性二级信使。迄今为止的研究主要集中在理解和靶向 Jak3 在免疫中的细胞自主作用，而 Jak3 在造血系统外的功能表达在很大程度上仍未被报道。我们表明，Jak3 在造血和非造血器官的血管内皮细胞中表达，在骨髓中表达水平更高。骨髓龛被理解为调节造血功能的不同细胞类型的网络。我们表明，Jak3 骨髓龛对长期重建造血干细胞 (LT-HSCs) 的维持是有害的，并且高表达 Jak3 的内皮细胞在体外具有增加 LT-HSCs 扩增的潜力。这项工作可能有助于确定在骨髓血管龛中高度特异性酪氨酸激酶的新功能，并进一步表征窦状内皮细胞的 LT-HSC 功能。
