Regulation of murine normal and stress-induced erythropoiesis by Desert Hedgehog
Regulation of murine normal and stress-induced erythropoiesis by Desert Hedgehog
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DOI：
10.1182/blood-2011-10-387266
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发表时间：
2012-05-17
期刊：
影响因子：
20.3
通讯作者：
Crompton, Tessa
中科院分区：
文献类型：
--
作者：
Lau, Ching-in;Outram, Susan V.;Crompton, Tessa
Hedgehog 信号在造血过程中的功能存在争议，不同的实验系统给出了相反的结果。在这里，我们研究了 Desert Hedgehog (Dhh) 在调节小鼠红细胞生成中的作用。 Dhh 是 3 种哺乳动物 Hedgehog 家族蛋白之一。 Dhh 对于睾丸发育和雪旺细胞功能至关重要。通过对 Dhh 缺陷小鼠的分析，我们发现 Dhh 负向调节红细胞分化的多个阶段。与野生型（WT）相比，在Dhh缺陷的骨髓中，共同髓系祖细胞（CMP）数量增加，但从CMP向粒细胞/巨噬细胞祖细胞的分化减少，并且成熟粒细胞数量减少。相反，从CMP向巨核细胞/红细胞祖细胞的分化增加，并且巨核细胞/红细胞祖细胞群增加。此外，我们发现成红细胞群体在体外和离体条件下均具有 Dhh 反应性，并且 Dhh 负向调节成红细胞分化。在 Dhh 缺乏的脾脏和骨髓中，与 WT 相比，BFU-E 和成红细胞数量增加。在辐射后造血恢复期间，以及在应激诱导红细胞生成的条件下，与WT相比，Dhh缺陷小鼠的脾脏和骨髓中红细胞分化加速。 （血。2012；119（20）：4741-4751）
The function of Hedgehog signaling in hematopoiesis is controversial, with different experimental systems giving opposing results. Here we examined the role of Desert Hedgehog (Dhh) in the regulation of murine erythropoiesis. Dhh is one of 3 mammalian Hedgehog family proteins. Dhh is essential for testis development and Schwann cell function. We show, by analysis of Dhh-deficient mice, that Dhh negatively regulates multiple stages of erythrocyte differentiation. In Dhh-deficient bone marrow, the common myeloid progenitor (CMP) population was increased, but differentiation from CMP to granulocyte/macrophage progenitor was decreased, and the mature granulocyte population was decreased, compared with wild-type (WT). In contrast, differentiation from CMP to megakaryocyte/erythrocyte progenitor was increased, and the megakaryocyte/erythrocyte progenitor population was increased. In addition, we found that erythroblast populations were Dhh-responsive in vitro and ex vivo and that Dhh negatively regulated erythroblast differentiation. In Dhh-deficient spleen and bone marrow, BFU-Es and erythroblast populations were increased compared with WT. During recovery of hematopoiesis after irradiation, and under conditions of stress-induced erythropoiesis, erythrocyte differentiation was accelerated in both spleen and bone marrow of Dhh-deficient mice compared with WT. (Blood. 2012; 119(20):4741-4751)