Cell-specific ablation in the testis: what have we learned?

Cell-specific ablation in the testis: what have we learned?
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DOI:
10.1111/andr.12107
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发表时间:
2015-11
期刊:
影响因子:
4.5
通讯作者:
Rebourcet D
Rebourcet D
中科院分区:
医学2区
文献类型:
--
作者:
Smith LB;O'Shaughnessy PJ;Rebourcet D

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睾丸的发育和功能是多种细胞类型之间自分泌、旁分泌和内分泌相互作用的复杂过程的顶点。剖析这一点通常涉及使用系统性治疗来扰乱内分泌功能,或者最近使用转基因模型来敲除单个基因。然而,一次靶向一个基因并不能完全捕获每种细胞类型的更广泛的作用。一种经常被忽视但非常强大的阐明细胞功能的方法是使用细胞消融策略,特别是去除一个细胞群并检查对发育和功能的影响。细胞消融研究揭示了细胞间相互作用的更全面的概述。这不仅确定了消融细胞类型的重要作用,这保证了进一步的下游研究,而且重要的是,揭示了组织内完全独立于消融细胞类型发生的功能。迄今为止,睾丸中的细胞消融研究已经专门去除了生殖细胞、间质细胞、巨噬细胞和最近的支持细胞。这些研究提供了通过其他方法无法理解的巨大飞跃;因此,细胞消融是研究人员工具包中的重要组成部分,应该被视为对更主流方法的补充,以促进我们对睾丸生物学的理解。在这篇综述中,我们总结了睾丸中使用的细胞消融模型,并讨论了这些模型中的每一个都教会了我们睾丸的发育和功能。
Testicular development and function is the culmination of a complex process of autocrine, paracrine and endocrine interactions between multiple cell types. Dissecting this has classically involved the use of systemic treatments to perturb endocrine function, or more recently, transgenic models to knockout individual genes. However, targeting genes one at a time does not capture the more wide‐ranging role of each cell type in its entirety. An often overlooked, but extremely powerful approach to elucidate cellular function is the use of cell ablation strategies, specifically removing one cellular population and examining the resultant impacts on development and function. Cell ablation studies reveal a more holistic overview of cell–cell interactions. This not only identifies important roles for the ablated cell type, which warrant further downstream study, but also, and importantly, reveals functions within the tissue that occur completely independently of the ablated cell type. To date, cell ablation studies in the testis have specifically removed germ cells, Leydig cells, macrophages and recently Sertoli cells. These studies have provided great leaps in understanding not possible via other approaches; as such, cell ablation represents an essential component in the researchers’ tool‐kit, and should be viewed as a complement to the more mainstream approaches to advancing our understanding of testis biology. In this review, we summarise the cell ablation models used in the testis, and discuss what each of these have taught us about testis development and function.