Endothelial Jak3 expression enhances pro-hematopoietic angiocrine function in mice.
Endothelial Jak3 expression enhances pro-hematopoietic angiocrine function in mice.
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DOI：
10.1038/s42003-021-01846-3
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发表时间：
2021-03-25
影响因子：
5.9
通讯作者：
Lis R
中科院分区：
文献类型：
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作者：
Barcia Durán JG;Lu T;Houghton S;Geng F;Schreiner R;Xiang J;Rafii S;Redmond D;Lis R
Jak 3是Jak家族中唯一一个非混杂的二级信使。迄今为止的研究集中在理解和靶向Jak 3在免疫中的细胞自主作用，而造血系统外的功能性Jak 3表达在很大程度上仍未报道。我们发现Jak 3在造血和非造血器官的内皮细胞中表达，在骨髓中表达增强。骨髓小生境被理解为调节造血功能的不同细胞类型的网络。我们发现，JAK 3-/-骨髓小生境对维持长期再生造血干细胞（LT-HSC）是有害的，并且JAK 3过表达的内皮细胞在体外扩增LT-HSC的潜力增加。这项工作可能有助于确定一种高度特异性的酪氨酸激酶在骨髓血管龛中的新功能，并进一步表征窦内皮的LT-HSC功能。Barcia Durán等人表明酪氨酸激酶基因Jak 3在小鼠的多种内皮细胞类型中表达，包括在非造血器官中，在骨髓中表达特别高。使用缺乏Jak 3的小鼠，他们表明在骨髓龛中表达的Jak 3对于维持长期再生造血干细胞很重要。
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 Durán 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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影响因子：
23.9
作者：
Butler JM;Nolan DJ;Vertes EL;Varnum-Finney B;Kobayashi H;Hooper AT;Seandel M;Shido K;White IA;Kobayashi M;Witte L;May C;Shawber C;Kimura Y;Kitajewski J;Rosenwaks Z;Bernstein ID;Rafii S
通讯作者：
Rafii S
影响因子：
64.5
作者：
Baryawno, Ninib;Przybylski, Dariusz;Scadden, David T.
通讯作者：
Scadden, David T.
影响因子：
21.3
作者：
Asada N;Kunisaki Y;Pierce H;Wang Z;Fernandez NF;Birbrair A;Ma'ayan A;Frenette PS
通讯作者：
Frenette PS
影响因子：
2.5
作者：
Alva, JA;Zovein, AC;Iruela-Arispe, ML
通讯作者：
Iruela-Arispe, ML
影响因子：
82.9
作者：
通讯作者：
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