Human haematopoietic stem/progenitor cells express several functional sex hormone receptors.
Human haematopoietic stem/progenitor cells express several functional sex hormone receptors.
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DOI：
10.1111/jcmm.12712
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发表时间：
2016-01
影响因子：
5.3
通讯作者：
Ratajczak MZ
中科院分区：
文献类型：
--
作者：
Abdelbaset-Ismail A;Suszynska M;Borkowska S;Adamiak M;Ratajczak J;Kucia M;Ratajczak MZ
越来越多的证据表明，小鼠造血干细胞/祖细胞(HSPC)与生殖系有几个共同的标记，最近的报道支持这种联系，即垂体和性腺性激素(SexHs)调节小鼠HSPC的发育。也有报道称，人类HSPC和它们的小鼠一样，对某些性激素(如雄激素)有反应。然而，为了更好地阐明性激素，特别是脑垂体性激素对人类造血的影响，我们测试了从人脐血(UCB)和外周血(PB)纯化的HSPC上垂体性激素受体(包括卵泡刺激素(FSH)、黄体生成素(LH)和催乳素(PRL))以及性腺性激素受体(包括孕酮、雌激素和雄激素)的表达。然后，我们在体外信号转导研究和体外克隆形成试验中测试了这些受体的功能。同时，我们检测了性激素对人骨髓间充质干细胞(MSCs)的影响。最后，基于我们观察到至少部分脐带血来源的CD45HSPC分化为CD45HSPC的极小胚胎样干细胞(VSEL)，我们还研究了这些细胞上垂体和性腺−受体的表达。我们首次报道了人类HSPC和VSEL和它们的小鼠一样，在mRNA和蛋白水平上表达垂体和性腺SexH受体。最重要的是，SexH如果添加到次适剂量的造血细胞因子和生长因子中，可以促进人HSPC的克隆生长，并直接刺激MSCs的增殖。
Evidence has accumulated that murine haematopoietic stem/progenitor cells (HSPCs) share several markers with the germline, a connection supported by recent reports that pituitary and gonadal sex hormones (SexHs) regulate development of murine HSPCs. It has also been reported that human HSPCs, like their murine counterparts, respond to certain SexHs (e.g. androgens). However, to better address the effects of SexHs, particularly pituitary SexHs, on human haematopoiesis, we tested for expression of receptors for pituitary SexHs, including follicle‐stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL), as well as the receptors for gonadal SexHs, including progesterone, oestrogens, and androgen, on HSPCs purified from human umbilical cord blood (UCB) and peripheral blood (PB). We then tested the functionality of these receptors in ex vivo signal transduction studies and in vitro clonogenic assays. In parallel, we tested the effect of SexHs on human mesenchymal stromal cells (MSCs). Finally, based on our observation that at least some of the UCB‐derived, CD45− very small embryonic‐like stem cells (VSELs) become specified into CD45+ HSPCs, we also evaluated the expression of pituitary and gonadal SexH receptors on these cells. We report for the first time that human HSPCs and VSELs, like their murine counterparts, express pituitary and gonadal SexH receptors at the mRNA and protein levels. Most importantly, SexH if added to suboptimal doses of haematopoietic cytokines and growth factors enhance clonogenic growth of human HSPCs as well as directly stimulate proliferation of MSCs.