Nature2014-06-26 5:29 PM

造血干细胞的雌雄差别 Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy

论文摘要 

干细胞被长距离信号相对于被组织内的局部信号调控的程度是干细胞生物学中一个基本问题。很多研究工作都集中在干细胞龛是怎样对组织内的局部信号做出反应的。但在饥饿或怀孕等条件下,系统信号可能将调制多种组织中的干细胞功能,而这项研究显示了雌激素对怀孕小鼠的造血干细胞的一个长距离影响。作者利用一种遗传方法发现,造血干细胞刺激(这会有助于母亲去满足增加的造血需求)取决于雌激素受体(ER()的表达。荷尔蒙水平在雄性和雌性中是不同的,但造血干细胞也是这样:响应于雌激素,雌性小鼠干细胞的分裂频率要显著高于雄性小鼠的干细胞。

Abstract 

Sexually dimorphic mammalian tissues, including sexual organs and the brain, contain stem cells that are directly or indirectly regulated by sex hormones. An important question is whether stem cells also exhibit sex differences in physiological function and hormonal regulation in tissues that do not show sex-specific morphological differences. The terminal differentiation and function of some haematopoietic cells are regulated by sex hormones, but haematopoietic stem-cell function is thought to be similar in both sexes. Here we show that mouse haematopoietic stem cells exhibit sex differences in cell-cycle regulation by oestrogen. Haematopoietic stem cells in female mice divide significantly more frequently than in male mice. This difference depends on the ovaries but not the testes. Administration of oestradiol, a hormone produced mainly in the ovaries, increased haematopoietic stem-cell division in males and females. Oestrogen levels increased during pregnancy, increasing haematopoietic stem-cell division, haematopoietic stem-cell frequency, cellularity, and erythropoiesis in the spleen. Haematopoietic stem cells expressed high levels of oestrogen receptor-α (ERα). Conditional deletion of ERα from haematopoietic stem cells reduced haematopoietic stem-cell division in female, but not male, mice and attenuated the increases in haematopoietic stem-cell division, haematopoietic stem-cell frequency, and erythropoiesis during pregnancy. Oestrogen/ERα signalling promotes haematopoietic stem-cell self-renewal, expanding splenic haematopoietic stem cells and erythropoiesis during pregnancy.

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