Unified single-cell analysis of testis gene regulation and pathology in five mouse strains

Min Jung, Daniel Wells, Jannette Rusch, Suhaira Ahmad, Jonathan Marchini, Simon R. Myers, Don Conrad

Research output: Contribution to journalArticle

10 Scopus citations

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 analyze 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 analyzing mutant and wild-type cells we decomposed our data into 46 components that identify novel meiotic gene-regulatory programs, 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.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Jun 25 2019

Keywords

  • computational biology
  • factor analysis
  • gene regulation
  • genetics
  • genomics
  • infertility
  • meiosis
  • mouse
  • single-cell
  • systems biology
  • testis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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