Cell Stem Cell:精子究竟如何发育?

2017-10-17 Lucy,Juka 转化医学网

犹他大学亨斯迈癌症研究所(HCI)与犹他大学卫生院(U of U Health)的科学家在一项最新的研究中揭示了人类精子干细胞发育过程中发生的复杂过程。


犹他大学亨斯迈癌症研究所(HCI)与犹他大学卫生院(U of U Health)的科学家在一项最新的研究中揭示了人类精子干细胞发育过程中发生的复杂过程。

这是迄今为止首个描述人类精子干细胞成熟后所经历变化的研究。

研究结果对于理解男性不育症和癌症的发展具有重要意义。详细内容发表在Cell Stem Cell期刊上,题为“Transcription, Signaling and Metabolic Transitions During Human Spermatogonial Stem Cell Differentiation”。

既往关于精子干细胞的研究仅限于包括小鼠在内的动物模型中。而在这项首个关于人类精子干细胞发育的研究中,科学家发现,人类中精子干细胞的发育过程比之前所理解的要复杂的多。通过使用基因组分析工具,科学家成功的描绘出了精子干细胞在其正常发育过程中所经历的多阶段过程。

研究第一作者——HCI基础科学的高级主管,犹他大学肿瘤学教授Bradley Cairns博士强调:“这些信息为正常情况下精子干细胞的发育以及功能的发挥提供了全新的见解。借此,我们构建了一个意义十分重大的流程框架图,现在我们可以利用这个模式框架来帮助我们掌握:究竟是哪个环节出了问题,从而导致了男性的不孕和癌症。"

研究中,科研人员逐个检查在正常发育过程中每个给定细胞中所有“开启”或者“关闭”的基因。通过单细胞RNA测序分析技术,Cairns博士的实验室对每个细胞进行单独分析,并建立了人精子干细胞的基因表达谱。

在他们的研究结果中,他们详尽的描述了精子干细胞成熟的四个重要不同细胞周期,并揭示了干细胞如何从“沉寂”状态进入到干细胞分化期间的“增殖”状态,至最终成熟“分化”为精子。此外,研究数据还明确指明在细胞的不同阶段,细胞周期调节因子、转录因子和信号因子等均发生了的不同程度的转变。

研究共同作者——泌尿生殖科医师、犹他大学卫生院外科助理教授James Hotaling博士谈到:“患者被确诊为不孕不育症,这对于整个家庭都是一次沉痛的打击。而这项研究可以实实在在的帮助我们了解不孕的某些原因。”同时,Cairns博士认为:“研究结果也能帮助我们了解一些癌症是如何发生的,已知不孕症的男性患上某些癌症(如睾丸癌或前列腺癌)的风险会更高,而在这项研究中国我们揭示了基因在精子干细胞的发育过程中所发挥的具体作用,接下来我们的研究将着眼于利用这些知识来更好的了解当精子干细胞发育不正常而转化为癌细胞时,基因发生了什么样的变化。”

在此,我们有理由相信,研究结果将有助于未来为临床工作者提供更好的用于男性不育症诊断和治疗的工具,不仅如此,这项研究对于揭示男性不育相关的癌症其复杂的遗传变化也具有非凡的意义。

原始出处:

Guo J1, Grow EJ1, Yi C1,et al.Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development.Cell Stem Cell. 2017 Oct 5;21(4):533-546.e6. doi: 10.1016/j.stem.2017.09.003.

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    2017-12-27 维他命
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    2017-10-19 neurowu
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    2017-10-17 137****9095

    henhao

    0

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