Unified single-cell analysis of testis gene regulation and pathology in 5 mouse strains
- Washington University School of Medicine, United States
- University of Oxford, United Kingdom
- Oregon Health and Science University, United States
Abstract
To fully exploit the potential of single-cell functional genomics in the study of development and disease, robust methods are needed to simplify the analysis of data across samples, time-points and individuals. Here we introduce a model-based factor analysis method, SDA, to analyse a novel 57,600-cell dataset from the testes of wild-type mice and mice with gonadal defects due to disruption of the genes Mlh3, Hormad1, Cul4a or Cnp. By jointly analysing mutant and wild-type cells we decomposed our data into 46 components that identify novel meiotic gene-regulatory programmes, mutant-specific pathological processes, and technical effects, and provide a framework for imputation. We identify, de novo, DNA sequence motifs associated with individual components that define temporally varying modes of gene expression control. Analysis of SDA components also led us to identify a rare population of macrophages within the seminiferous tubules of Mlh3-/- and Hormad1-/- mice, an area typically associated with immune privilege.
Data availability
Raw data and processed files for Drop-seq and 10X Genomics experiments are available in GEO under accession number: GSE113293
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A single-cell atlas of testis gene expression from 5 mouse strainsNCBI Gene Expression Omnibus, GSE113293.
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Novel Insights into the Downstream Pathways and Targets Controlled by Transcription Factors CREM in the TestisPLoS One, doi:10.1371/journal.pone.0031798.s009.
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RFX2 Is a Major Transcriptional Regulator of Spermiogenesis.PLoS Genetics, doi:10.1371/journal.pgen.1005368.s011.
Article and author information
Author details
Funding
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD078641)
- Donald F Conrad
National Institute of Mental Health (R01MH101810)
- Donald F Conrad
Wellcome (098387/Z/12/Z)
- Simon R Myers
Wellcome (109109/Z/15/Z)
- Daniel Wells
European Research Council (617306)
- Jonathan Marchini
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Deborah Bourc'his, Institut Curie, France
Ethics
Animal experimentation: All animal experiments were performed in compliance with the regulations of the Animal Studies Committee at Washington University in St. Louis under approved protocol #20160089.
Version history
- Received: November 28, 2018
- Accepted: June 17, 2019
- Accepted Manuscript published: June 25, 2019 (version 1)
- Version of Record published: July 9, 2019 (version 2)
Copyright
© 2019, Jung et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Unified single-cell analysis of testis gene regulation and pathology in 5 mouse strains
eLife 8:e43966.
https://doi.org/10.7554/eLife.43966
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