Hematopoietic Stem/Progenitor Cells Express Several Functional Sex Hormone Receptors-Novel Evidence for a Potential Developmental Link Between Hematopoiesis and Primordial Germ Cells
Hematopoietic Stem/Progenitor Cells Express Several Functional Sex Hormone Receptors-Novel Evidence for a Potential Developmental Link Between Hematopoiesis and Primordial Germ Cells
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DOI：
10.1089/scd.2014.0546
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发表时间：
2015-04-15
影响因子：
4
通讯作者：
Ratajczak, Mariusz Z.
中科院分区：
文献类型：
--
作者：
Mierzejewska, Katarzyna;Borkowska, Sylwia;Ratajczak, Mariusz Z.
越来越多的证据表明，造血干细胞（HSPCs）与生殖系有几个共同的标记，催乳素、雄激素和雌激素刺激造血的报道支持了这一联系。为了更直接地解决这个问题，我们测试了垂体源性激素受体的表达，如促卵泡激素（FSH）和促黄体生成素（LH），在纯化的小鼠骨髓（BM）细胞中富集HSPCs，并在体外信号转导研究和体外克隆实验中测试了这些受体的功能。我们还测试了垂体和性腺来源的性激素（SexHs）是否会增加溴脱氧尿苷（BrdU）在小鼠造血干细胞中的掺入和造血克隆祖细胞的扩增，并促进亚致死辐照动物血细胞计数的恢复。我们首次报道了HSPCs表达功能性FSH和LH受体，并在体内和体外响应垂体SexHs刺激增殖。此外，根据我们的观察，至少有一些CD45（-）非常小的胚胎样干细胞（VSELs）可能被指定为CD45(+) HSPCs，我们还评估了这些细胞上垂体和性腺SexHs受体的表达，并测试了这些静止细胞是否会在体内对SexHs给予反应而扩增。我们发现血管内皮细胞表达SexHs受体，并在体内对SexHs刺激作出反应，BrdU积累证明了这一点。由于至少一些血管内皮细胞具有迁移原始生殖细胞的几个特征标记，并且可以被指定为HSPCs，这一观察结果为骨髓干细胞的层次结构提供了新的思路。
Evidence has accumulated that hematopoietic stem progenitor cells (HSPCs) share several markers with the germline, a connection supported by reports that prolactin, androgens, and estrogens stimulate hematopoiesis. To address this issue more directly, we tested the expression of receptors for pituitary-derived hormones, such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH), on purified murine bone marrow (BM) cells enriched for HSPCs and tested the functionality of these receptors in ex vivo signal transduction studies and in vitro clonogenic assays. We also tested whether administration of pituitary- and gonad-derived sex hormones (SexHs) increases incorporation of bromodeoxyuridine (BrdU) into HSPCs and expansion of hematopoietic clonogenic progenitors in mice and promotes recovery of blood counts in sublethally irradiated animals. We report for the first time that HSPCs express functional FSH and LH receptors and that both proliferate in vivo and in vitro in response to stimulation by pituitary SexHs. Furthermore, based on our observations that at least some of CD45(-) very small embryonic-like stem cells (VSELs) may become specified into CD45(+) HSPCs, we also evaluated the expression of pituitary and gonadal SexHs receptors on these cells and tested whether these quiescent cells may expand in vivo in response to SexHs administration. We found that VSELs express SexHs receptors and respond in vivo to SexHs stimulation, as evidenced by BrdU accumulation. Since at least some VSELs share several markers characteristic of migrating primordial germ cells and can be specified into HSPCs, this observation sheds new light on the BM stem cell hierarchy.