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人类性腺发育的单细胞路线图问世
2022-07-10 14:13
来源：小柯机器人

英国威康桑格研究所Roser Vento-Tormo小组绘制出人类性腺发育的单细胞路线图。该项研究成果于2022年7月6日在线发表在《自然》杂志上。

通过使用单细胞和空间转录组学、染色质可及性检测和荧光显微镜的组合，研究人员生成了第一和第二孕期人类性腺的综合图谱。通过对小鼠同等发育阶段的分析，研究人员提取了控制生殖细胞和体细胞系发育的人类特异性调控方案。在这两个物种中，研究人员定义了在性别特化时存在的体细胞状态，包括双能的早期支持群体，在雄性中，它上调睾丸决定因子SRY和sPAX8s，一个位于性腺-小肠界面的性腺系。
 
在雌性中，研究人员解析了产生第一和第二波颗粒细胞的细胞和分子事件，这些细胞将发育中的卵巢分隔开来以调节生殖细胞的分化。在雄性中，研究人员确定了人类SIGLEC15+和TREM2+的胎儿睾丸巨噬细胞，它们分别向发育中的睾丸索外部和内部的体细胞发出信号。这项研究提供了人类和小鼠性腺分化的全面时空图，可以指导体外性腺的发生。
 
据介绍，性腺发育是一个复杂的过程，包括性别的确定，然后是不同的成熟，变成睾丸或卵巢。历史上，有限的组织可及性、缺乏可靠的体外模型以及人类和小鼠之间的关键差异阻碍了人们对人类性腺发育的了解，尽管它在性腺状况和不孕不育中具有重要意义。
 
附：英文原文
 
Title: Single-cell roadmap of human gonadal development

Author: Garcia-Alonso, Luz, Lorenzi, Valentina, Mazzeo, Cecilia Icoresi, Alves-Lopes, Joo Pedro, Roberts, Kenny, Sancho-Serra, Carmen, Engelbert, Justin, Marekov, Magda, Gruhn, Wolfram H., Botting, Rachel A., Li, Tong, Crespo, Berta, van Dongen, Stijn, Kiselev, Vladimir Yu, Prigmore, Elena, Herbert, Mary, Moffett, Ashley, Chdotal, Alain, Bayraktar, Omer Ali, Surani, Azim, Haniffa, Muzlifah, Vento-Tormo, Roser

Issue&Volume: 2022-07-06

Abstract: Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries1. Historically, limited tissue accessibility, a lack of reliable in vitro models and critical differences between humans and mice have hampered our knowledge of human gonadogenesis, despite its importance in gonadal conditions and infertility. Here, we generated a comprehensive map of first- and second-trimester human gonads using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy. We extracted human-specific regulatory programmes that control the development of germline and somatic cell lineages by profiling equivalent developmental stages in mice. In both species, we define the somatic cell states present at the time of sex specification, including the bipotent early supporting population that, in males, upregulates the testis-determining factor SRY and sPAX8s, a gonadal lineage located at the gonadal–mesonephric interface. In females, we resolve the cellular and molecular events that give rise to the first and second waves of granulosa cells that compartmentalize the developing ovary to modulate germ cell differentiation. In males, we identify human SIGLEC15+ and TREM2+ fetal testicular macrophages, which signal to somatic cells outside and inside the developing testis cords, respectively. This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, which can guide in vitro gonadogenesis.

DOI: 10.1038/s41586-022-04918-4

Source: https://www.nature.com/articles/s41586-022-04918-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html


本期文章：《自然》：Online/在线发表

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