Dissecting mammalian spermatogenesis using spatial transcriptomics.
Dissecting mammalian spermatogenesis using spatial transcriptomics.
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利用空间转录组学剖析哺乳动物精子发生。
DOI：
10.1016/j.celrep.2021.109915
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发表时间：
2021-11-02
期刊：
影响因子：
8.8
通讯作者：
Chen F
中科院分区：
文献类型：
--
作者：
Chen H;Murray E;Sinha A;Laumas A;Li J;Lesman D;Nie X;Hotaling J;Guo J;Cairns BR;Macosko EZ;Cheng CY;Chen F
单细胞RNA测序揭示了调控哺乳动物精子发生的基因程序中广泛的分子多样性，但未能在生精小管的天然背景下描绘它们的动态，生精小管是精子发生的空间受限功能单位。在这里，我们使用空间转录学技术Slide-seq来生成一个图谱，该图谱以接近单细胞的分辨率捕捉小鼠和人类睾丸的空间基因表达模式。利用Slide-Seq数据，我们设计了一个计算框架，可以准确地定位单个生精小管中的睾丸细胞类型。无偏分析系统地识别空间模式的基因和基因程序。结合Slide-Seq和靶向原位RNA测序，我们发现小鼠和人类睾丸的精原微环境的细胞组成存在显著差异。最后，对野生型和糖尿病小鼠睾丸的空间图谱的比较表明，生精小管空间细胞组织的破坏是糖尿病导致男性不育的潜在机制。Chen等人以接近单细胞的分辨率生成哺乳动物睾丸的空间转录组图谱，通过准确定位睾丸细胞类型和重建组织结构来重述精子发生。该图谱用于揭示睾丸微环境的空间组织，并描绘其在糖尿病条件下的变化。
Single-cell RNA sequencing has revealed extensive molecular diversity in gene programs governing mammalian spermatogenesis but fails to delineate their dynamics in the native context of seminiferous tubules, the spatially confined functional units of spermatogenesis. Here, we use Slide-seq, a spatial transcriptomics technology, to generate an atlas that captures the spatial gene expression patterns at near-single-cell resolution in the mouse and human testis. Using Slide-seq data, we devise a computational framework that accurately localizes testicular cell types in individual seminiferous tubules. Unbiased analysis systematically identifies spatially patterned genes and gene programs. Combining Slide-seq with targeted in situ RNA sequencing, we demonstrate significant differences in the cellular compositions of spermatogonial microenvironment between mouse and human testes. Finally, a comparison of the spatial atlas generated from the wild-type and diabetic mouse testis reveals a disruption in the spatial cellular organization of seminiferous tubules as a potential mechanism of diabetes-induced male infertility. Chen et al. generate a spatial transcriptome atlas of the mammalian testis at near-single-cell resolution that recapitulates spermatogenesis by accurately localizing testicular cell types and reconstructing tissue structures. The atlas is used to reveal the spatial organization of testicular microenvironment and profile its changes under diabetic conditions.
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影响因子：
44.1
作者：
Guo J;Grow EJ;Mlcochova H;Maher GJ;Lindskog C;Nie X;Guo Y;Takei Y;Yun J;Cai L;Kim R;Carrell DT;Goriely A;Hotaling JM;Cairns BR
通讯作者：
Cairns BR
影响因子：
8.8
作者：
DeFalco T;Potter SJ;Williams AV;Waller B;Kan MJ;Capel B
通讯作者：
Capel B
影响因子：
11.8
作者：
Green CD;Ma Q;Manske GL;Shami AN;Zheng X;Marini S;Moritz L;Sultan C;Gurczynski SJ;Moore BB;Tallquist MD;Li JZ;Hammoud SS
通讯作者：
Hammoud SS
影响因子：
3.6
作者：
Griswold MD
通讯作者：
Griswold MD
影响因子：
--
作者：
Bhat, GK;Sea, TL;Mann, DR
通讯作者：
Mann, DR