2019/06/25 by Min Jung, Daniel Wells, Jannette Rusch +4 · 1 citation
Biochemistry, Genetics and Molecular Biology · #Epigenetics and DNA Methylation #Single-cell and spatial transcriptomics #RNA Research and Splicing
paper · doi:10.7554/elife.43966
openalex publication_date 2019/06/25 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.