JAK1 is a critical effector of pro-inflammatory cytokine signaling and plays important roles in immune function, while abnormal JAK1 activity has been linked to immunological and neoplastic diseases. Specific functions of JAK1 in the context of hematopoiesis, and specifically within hematopoietic stem cells (HSCs), have not clearly been delineated. Here, we show that conditional Jak1 loss in HSCs reduces their self-renewal and markedly alters lymphoid/myeloid differentiation in vivo. Jak1-deficient HSCs exhibit decreased competitiveness in vivo and are unable to rescue hematopoiesis in the setting of myelosuppression. They exhibit increased quiescence, an inability to enter the cell cycle in response to hematopoietic stress, and a marked reduction in cytokine sensing, including in response to type I interferons and IL-3. Moreover, Jak1 loss is not fully rescued by expression of a constitutively active Jak2 allele. Together, these data highlight an essential role for Jak1 in HSC homeostasis and stress responses.

中文翻译：

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Jak1整合了细胞因子传感，以调节造血干细胞功能和应激造血功能。

JAK1是促炎性细胞因子信号传导的关键效应子，在免疫功能中起着重要作用，而异常的JAK1活性则与免疫学和肿瘤性疾病有关。在造血的背景下，特别是在造血干细胞（HSC）中，JAK1的特定功能尚未明确描述。在这里，我们显示HSC中有条件的Jak1丢失减少了它们的自我更新，并显着改变了体内的淋巴/髓系分化。缺乏Jak1的HSC在体内表现出降低的竞争力，并且在骨髓抑制的情况下无法挽救造血功能。它们表现出增加的静止性，对造血应激的响应而无法进入细胞周期以及细胞因子感测的显着降低，包括对I型干扰素和IL-3的响应。而且，通过组成性活跃的Jak2等位基因的表达不能完全挽救Jak1的丢失。总之，这些数据突显了Jak1在HSC稳态和应激反应中的重要作用。