A Comprehensive Roadmap of Murine Spermatogenesis Defined by Single-Cell RNA-Seq

Christopher Daniel Green; Qianyi Ma; Gabriel L Manske; Adrienne Niederriter Shami; Xianing Zheng; Simone Marini; Lindsay Moritz; Caleb Sultan; Stephen J Gurczynski; Bethany B Moore; Michelle D Tallquist; Jun Z Li; Saher Sue Hammoud

doi:10.1016/j.devcel.2018.07.025

A Comprehensive Roadmap of Murine Spermatogenesis Defined by Single-Cell RNA-Seq

Dev Cell. 2018 Sep 10;46(5):651-667.e10. doi: 10.1016/j.devcel.2018.07.025. Epub 2018 Aug 23.

Affiliations

¹ Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
² Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA.
³ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
⁵ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
⁶ University of Hawaii Cardiovascular Center, Honolulu, HI, USA.
⁷ Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. Electronic address: junzli@med.umich.edu.
⁸ Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan, Ann Arbor, MI, USA. Electronic address: hammou@med.umich.edu.

Abstract

Spermatogenesis requires intricate interactions between the germline and somatic cells. Within a given cross section of a seminiferous tubule, multiple germ and somatic cell types co-occur. This cellular heterogeneity has made it difficult to profile distinct cell types at different stages of development. To address this challenge, we collected single-cell RNA sequencing data from ∼35,000 cells from the adult mouse testis and identified all known germ and somatic cells, as well as two unexpected somatic cell types. Our analysis revealed a continuous developmental trajectory of germ cells from spermatogonia to spermatids and identified candidate transcriptional regulators at several transition points during differentiation. Focused analyses delineated four subtypes of spermatogonia and nine subtypes of Sertoli cells; the latter linked to histologically defined developmental stages over the seminiferous epithelial cycle. Overall, this high-resolution cellular atlas represents a community resource and foundation of knowledge to study germ cell development and in vivo gametogenesis.

Keywords: germ cell developmental trajectory; germ cell differentiation; heterogeneity; single-cell RNA-seq; spermatogenesis; spermatogonial stem cell; testis niche.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Cells, Cultured
Gene Expression Profiling
Gene Expression Regulation, Developmental*
High-Throughput Nucleotide Sequencing / methods*
Male
Mice
Sertoli Cells / cytology*
Sertoli Cells / metabolism
Single-Cell Analysis / methods*
Spermatogenesis*
Testis / cytology*
Testis / metabolism

A Comprehensive Roadmap of Murine Spermatogenesis Defined by Single-Cell RNA-Seq

Authors

Affiliations

Abstract

Publication types

MeSH terms

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