Dissecting mammalian spermatogenesis using spatial transcriptomics
Haiqi Chen,
Evan Murray,
Anubhav Sinha,
Anisha Laumas,
Jilong Li,
Daniel Lesman,
Xichen Nie,
Jim Hotaling,
Jingtao Guo,
Bradley R. Cairns,
Evan Z. Macosko,
C. Yan Cheng,
Fei Chen
Affiliations
Haiqi Chen
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Corresponding author
Evan Murray
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Anubhav Sinha
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute, MIT, Cambridge, MA 02139, USA; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA 02142, USA
Anisha Laumas
Harvard University, Cambridge, MA 02138, USA
Jilong Li
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Daniel Lesman
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Xichen Nie
Department of Oncological Sciences and Huntsman Cancer Institute, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Jim Hotaling
Department of Oncological Sciences and Huntsman Cancer Institute, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Jingtao Guo
Department of Oncological Sciences and Huntsman Cancer Institute, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Bradley R. Cairns
Department of Oncological Sciences and Huntsman Cancer Institute, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Evan Z. Macosko
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA
C. Yan Cheng
The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY, 10065, USA
Fei Chen
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Corresponding author
Summary: 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.
