Leydig cell stem cells: Identification, proliferation and differentiation.
Leydig cell stem cells: Identification, proliferation and differentiation.
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间质细胞干细胞：鉴定、增殖和分化
DOI：
10.1016/j.mce.2016.10.010
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发表时间：
2017-04-15
影响因子：
4.1
通讯作者：
Zirkin BR
中科院分区：
文献类型：
--
作者：
Chen H;Wang Y;Ge R;Zirkin BR
成体间质细胞是由出生后早期睾丸间质中的未分化间充质样干细胞（间质干细胞，SLC）发育而来。在成年睾丸的管周和血管周围也发现了假定的SLC。后一种细胞通常是静止的，在失去成体细胞后能够再生新的Leydig细胞。最近的研究已经确定了几种蛋白质标记物来识别这些细胞，包括巢蛋白，PDGFRα，COUP-TFII，CD 51和CD 90。我们已经表明，SLCs的增殖是由DHH，FGF 2，PDGFBB，激活素和PDGFAA刺激的。TGFβ、雄激素和PKA信号传导抑制增殖。SLCs向睾丸激素分泌型Leydig细胞的分化受DHH（Desert hedgehog）、锂诱导信号和激活素的正向调节;而受TGFβ、PDGFBB、FGF 2、Notch和Wnt信号的负向调节。DHH，本身，被发现诱导SLC分化为LH反应性类固醇生成细胞，这表明DHH在SLC向Leydig谱系的承诺中起着关键作用。这些研究共同解决了低周转干细胞在复杂的成人器官中的功能和调节，并且也具有治疗雄激素缺乏症的潜在应用。
Adult Leydig cells develop from undifferentiated mesenchymal-like stem cells (stem Leydig cells, SLCs) present in the interstitial compartment of the early postnatal testis. Putative SLCs also have been identified in peritubular and perivascular locations of the adult testis. The latter cells, which normally are quiescent, are capable of regenerating new Leydig cells upon the loss of the adult cells. Recent studies have identified several protein markers to identify these cells, including nestin, PDGFRα, COUP-TFII, CD51 and CD90. We have shown that the proliferation of the SLCs is stimulated by DHH, FGF2, PDGFBB, activin and PDGFAA. Suppression of proliferation occurred with TGFβ, androgen and PKA signaling. The differentiation of the SLCs into testosterone-producing Leydig cells was found to be regulated positively by DHH (Desert hedgehog), lithium-induced signaling and activin; and negatively by TGFβ, PDGFBB, FGF2, Notch and Wnt signaling. DHH, by itself, was found to induce SLC differentiation into LH-responsive steroidogenic cells, suggesting that DHH plays a critical role in the commitment of SLC into the Leydig lineage. These studies, taken together, address the function and regulation of low turnover stem cells in a complex, adult organ, and also have potential application to the treatment of androgen deficiency.