Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy.
Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy.
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作者：
性二型哺乳动物组织，包括性器官和大脑，含有直接或间接受性激素调节的干细胞。一个重要的问题是干细胞是否在生理功能和激素调节方面也表现出性别差异，而这些组织并不表现出性别特异性的形态差异。一些造血细胞的终末分化和功能受性激素调节，但造血干细胞（HSC）的功能被认为在两性中是相似的。在这里，我们表明，小鼠造血干细胞表现出性别差异的细胞周期调节雌激素。女性的HSC分裂频率明显高于男性。这种差异取决于卵巢而不是睾丸。雌二醇是一种主要在卵巢中产生的激素，它的施用增加了雄性和雌性的HSC细胞分裂。雌激素水平在妊娠期间增加，增加HSC分裂，HSC频率，细胞构成和脾脏中的红细胞生成。HSC表达高水平的雌激素受体α（ERα）。从HSC中有条件地缺失ERα可减少雌性而非雄性小鼠的HSC分裂，并减弱妊娠期间HSC分裂、HSC频率和红细胞生成的增加。雌激素/ERα信号转导促进HSC自我更新，在妊娠期间扩增脾HSC和红细胞生成。
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 exhibit sex-specific morphological differences. The terminal differentiation and function of some haematopoietic cells are regulated by sex hormones but haematopoietic stem cell (HSC) function is thought to be similar in both sexes. Here we show that mouse HSCs exhibit sex differences in cell cycle regulation by estrogen. HSCs in females divide significantly more frequently than in males. This difference depended on the ovaries but not the testes. Administration of estradiol, a hormone produced mainly in the ovaries, increased HSC cell division in males and females. Estrogen levels increased during pregnancy, increasing HSC division, HSC frequency, cellularity, and erythropoiesis in the spleen. HSCs expressed high levels of estrogen receptor α (ERα). Conditional deletion of ERα from HSCs reduced HSC division in female, but not male, mice and attenuated the increases in HSC division, HSC frequency, and erythropoiesis during pregnancy. Estrogen/ERα signaling promotes HSC self-renewal, expanding splenic HSCs and erythropoiesis during pregnancy.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
DOI：
10.1038/nri2394
发表时间：
2008-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Fish EN
通讯作者：
Fish EN
影响因子：
9.2
作者：
McLeod, Catherine J.;Wang, Lei;Wong, Chihunt;Jones, D. Leanne
通讯作者：
Jones, D. Leanne
影响因子：
64.8
作者：
Asselin-Labat, Marie-Liesse;Vaillant, Francois;Visvader, Jane E.
通讯作者：
Visvader, Jane E.
影响因子：
46.9
作者：
Foudi, Adlen;Hochedlinger, Konrad;Van Buren, Denille;Schindler, Jeffrey W.;Jaenisch, Rudolf;Carey, Vincent;Hock, Hanno
通讯作者：
Hock, Hanno