Single-cell roadmap of human gonadal development.
Single-cell roadmap of human gonadal development.
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人类性腺发育的单细胞路线图。
DOI：
10.1038/s41586-022-04918-4
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发表时间：
2022-07
期刊：
影响因子：
64.8
通讯作者：
Vento-Tormo, Roser
中科院分区：
文献类型：
--
作者：
Garcia-Alonso, Luz;Lorenzi, Valentina;Mazzeo, Cecilia Icoresi;Alves-Lopes, Joao Pedro;Roberts, Kenny;Sancho-Serra, Carmen;Engelbert, Justin;Mareckova, Magda;Gruhn, Wolfram H.;Botting, Rachel A.;Li, Tong;Crespo, Berta;van Dongen, Stijn;Kiselev, Vladimir Yu;Prigmore, Elena;Herbert, Mary;Moffett, Ashley;Chedotal, Alain;Bayraktar, Omer Ali;Surani, Azim;Haniffa, Muzlifah;Vento-Tormo, Roser
性腺发育是一个复杂的过程，涉及性别决定，然后分化成熟为睾丸或卵巢。从历史上看，有限的组织可及性，缺乏可靠的体外模型和人类和小鼠之间的关键差异阻碍了我们对人类性腺发生的了解，尽管它在性腺状况和不孕症中很重要。在这里，我们使用单细胞和空间转录组学，染色质可及性测定和荧光显微镜的组合产生了一个全面的地图的第一和第二孕期人类性腺。我们提取了人类特异性的调控程序，通过分析小鼠的等效发育阶段来控制生殖系和体细胞谱系的发育。在这两个物种中，我们定义的体细胞状态存在于性别规范的时间，包括双能早期支持人口，在男性中，上调睾丸决定因子SRY和sPAX 8 s，性腺谱系位于性腺-中肾界面。在女性中，我们解决了引起第一和第二波颗粒细胞的细胞和分子事件，这些颗粒细胞将发育中的卵巢区室化以调节生殖细胞分化。在男性中，我们鉴定了人SIGLEC 15+和TREM 2+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。本研究提供了一个全面的人类和小鼠性腺分化的时空图，可以指导体外性腺发生。这项研究提供了一个全面的时空地图的人类和小鼠性腺分化，使用单细胞和空间转录组学，染色质可及性测定和荧光显微镜，这可以指导体外性腺发育的组合。
Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries. 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. This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy, which can guide in vitro gonadogenesis.
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影响因子：
11.8
作者：
Elmentaite R;Ross ADB;Roberts K;James KR;Ortmann D;Gomes T;Nayak K;Tuck L;Pritchard S;Bayraktar OA;Heuschkel R;Vallier L;Teichmann SA;Zilbauer M
通讯作者：
Zilbauer M
影响因子：
30.8
作者：
Frattini, A;Orchard, PJ;Villa, A
通讯作者：
Villa, A
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
14.8
作者：
Efremova, Mirjana;Vento-Tormo, Miquel;Vento-Tormo, Roser
通讯作者：
Vento-Tormo, Roser
影响因子：
9.9
作者：
Gonzalez-Blas, Carmen Bravo;Quan, Xiao-Jiang;Aerts, Stein
通讯作者：
Aerts, Stein