Unified single-cell analysis of testis gene regulation and pathology in five mouse strains.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31237565.
- Also identified by DOI 10.7554/eLife.43966 and PMC identifier 6615865.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Mlh3</i>, <i>Hormad1</i>, <i>Cul4a</i> or <i>Cnp</i>. 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 <i>Mlh3<sup>-/-</sup></i> and <i>Hormad1<sup>-/-</sup></i> mice, an area typically associated with immune privilege.
Medical subject headings
- Cell Cycle Proteins
- MutL Proteins
- Spermatogenesis
- Testis