大鼠曲细精管微环境和miRNA对Leydig干细胞的调节机制研究

项目名称： 大鼠曲细精管微环境和miRNA对Leydig干细胞的调节机制研究

项目编号： No.31271252

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 陈浩林

作者单位： 温州医科大学

项目金额： 79万元

中文摘要： 睾丸Leydig干细胞（SLC）有潜力治疗睾酮缺乏症。 SLC的特点是具有自我更新和向睾丸Leydig细胞系分化的能力。一个基本的悬而未决的问题是如何造成SLC增生和向睾丸Leydig细胞分化。SLC自我更新和分化的调节需要微环境的外部信号和内在线索。我们最近的数据支持这一论点，即外层的曲细精管是SLC向Leydig细胞分化的关键微环境。内在的线索包括转录因子和miRNA。在此申请中，我们的目标是：1）确定SLC自我更新和向Leydig细胞系分化的微环境因子（包括PDGF和Wnt信号通路）; 2）确定转录因子如类固醇生长因子1（NR5A1）的甲基化状态和miRNA如何调节SLC的自我更新和分化。

中文关键词： 睾酮缺乏；睾丸间质干细胞；曲细精管培养；增殖；分化

英文摘要： Stem Leydig cells (SLC) have the potentials to be alternative therapy of testosterone deficiency (TD). The hallmark of SLC is their capability of self-renewing and of specifying into Leydig cell lineage. A fundamental unanswered question is how SLC are specified, maintained and instructed to differentiate into Leydig cells. Both external signals (SLC niche) and intrinsic cues are required to regulate the self-renewal and specification of SLC. Our recent data support the contention that the outer layer of the seminiferous tubule (ST) is a critical niche for SLC that specifies differentiation into cells of the ALC lineage in vitro. There also are intrinsic cues, including transcription factors and miRNAs that are involved in orchestrating SLC self-renewal and specification. Our goals in this application are to: 1) to determine how the niche controls SLC self-renewal/differentiation and how different extrinsic (niche) and/or systemic factors also contribute to amplifying SLC numbers and/or differentiation; 2) to determine how intrinsic cues, including transcription factors, methylation status of transcription factor steroidogenic factor 1 (NR5A1), and miRNAs regulate self-renewal and specification of SLCs.

英文关键词： Testosterone deficiency；Stem Leydig Cell;SLC；seminiferous tubule culture；proliferation；differentiation