Dissecting mammalian spermatogenesis using spatial transcriptomics

被引:80
作者
Chen, Haiqi [1 ]
Murray, Evan [1 ]
Sinha, Anubhav [1 ,2 ,3 ]
Laumas, Anisha [4 ]
Li, Jilong [1 ]
Lesman, Daniel [1 ]
Nie, Xichen [5 ,6 ]
Hotaling, Jim [5 ,6 ]
Guo, Jingtao [5 ,6 ]
Cairns, Bradley R. [5 ,6 ]
Macosko, Evan Z. [1 ,7 ]
Cheng, C. Yan [8 ]
Chen, Fei [1 ,9 ]
机构
[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
[2] MIT, McGovern Inst, Cambridge, MA 02139 USA
[3] Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02142 USA
[4] Harvard Univ, Cambridge, MA 02138 USA
[5] Univ Utah, Sch Med, Howard Hughes Med Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA
[6] Univ Utah, Sch Med, Howard Hughes Med Inst, Huntsman Canc Inst, Salt Lake City, UT 84112 USA
[7] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA
[8] Populat Council, Ctr Biomed Res, Mary M Wohlford Lab Male Contracept Res, New York, NY 10065 USA
[9] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
关键词
TO-PROTAMINE TRANSITION; GENE-EXPRESSION; SEMINIFEROUS EPITHELIUM; EPIGENETIC REGULATION; MEIOTIC REGULATION; DIABETES-MELLITUS; SERTOLI-CELLS; HISTONE; MOUSE; DYNAMICS;
D O I
10.1016/j.celrep.2021.109915
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页数:22
相关论文
共 50 条
[41]   Unravelling Prostate Cancer Heterogeneity Using Spatial Approaches to Lipidomics and Transcriptomics [J].
Mutuku, Shadrack M. ;
Spotbeen, Xander ;
Trim, Paul J. ;
Snel, Marten F. ;
Butler, Lisa M. ;
Swinnen, Johannes, V .
CANCERS, 2022, 14 (07)
[42]   Utilization of the QuPath open-source software platform for analysis of mammalian spermatogenesis† [J].
Niedenberger, Bryan A. ;
Belcher, Heather A. ;
Gilbert, Emma A. ;
Thomas, Matthew A. ;
Geyer, Christopher B. .
BIOLOGY OF REPRODUCTION, 2025, 112 (03) :583-599
[43]   Mechanisms regulating mammalian spermatogenesis and fertility recovery following germ cell depletion [J].
La, Hue M. ;
Hobbs, Robin M. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2019, 76 (20) :4071-4102
[44]   Characterization of the Nucleus Pulposus Progenitor Cells via Spatial Transcriptomics [J].
Chen, Yu ;
Zhang, Long ;
Shi, Xueqing ;
Han, Jie ;
Chen, Jingyu ;
Zhang, Xinya ;
Xie, Danlin ;
Li, Zan ;
Niu, Xing ;
Chen, Lijie ;
Yang, Chaoyong ;
Sun, Xiujie ;
Zhou, Taifeng ;
Su, Peiqiang ;
Li, Na ;
Greenblatt, Matthew B. ;
Ke, Rongqin ;
Huang, Jianming ;
Chen, Zhe-Sheng ;
Xu, Ren .
ADVANCED SCIENCE, 2024, 11 (18)
[45]   The promise of spatial transcriptomics for neuroscience in the era of molecular cell typing [J].
Lein, Ed ;
Borm, Lars E. ;
Linnarsson, Sten .
SCIENCE, 2017, 358 (6359) :64-+
[46]   A multiscale model via single-cell transcriptomics reveals robust patterning mechanisms during early mammalian embryo development [J].
Cang, Zixuan ;
Wang, Yangyang ;
Wang, Qixuan ;
Cho, Ken W. Y. ;
Holmes, William ;
Nie, Qing .
PLOS COMPUTATIONAL BIOLOGY, 2021, 17 (03)
[47]   Location, location, location: mapping the lymphoma tumor microenvironment using spatial transcriptomics [J].
Pickard, Keir ;
Stephenson, Emily ;
Mitchell, Alex ;
Jardine, Laura ;
Bacon, Chris M. .
FRONTIERS IN ONCOLOGY, 2023, 13
[48]   Cell Signaling Characterization for Spatial Transcriptomics (ST) Data Using Network Analysis [J].
Javaid, Azka ;
Frost, H. Robert .
COMPLEX NETWORKS & THEIR APPLICATIONS XIII, COMPLEX NETWORKS 2024-VOL 3, 2025, 1189 :394-405
[49]   A unified pipeline for FISH spatial transcriptomics [J].
Cisar, Cecilia ;
Keener, Nicholas ;
Ruffalo, Mathew ;
Paten, Benedict .
CELL GENOMICS, 2023, 3 (09)
[50]   Technical Advances and Applications of Spatial Transcriptomics [J].
Liang, Guohao ;
Yin, Hong ;
Ding, Fangyuan .
GEN BIOTECHNOLOGY, 2023, 2 (05) :384-398