Unified single-cell analysis of testis gene regulation and pathology in five mouse strains.
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.
['Jung|Min|M|', 'Wells|Daniel|D|0000-0002-2007-8978', 'Rusch|Jannette|J|', 'Ahmad|Suhaira|S|', 'Marchini|Jonathan|J|0000-0003-0610-8322', 'Myers|Simon R|SR|', 'Conrad|Donald F|DF|0000-0003-3828-8970']
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase D000818:Animals D018797:Cell Cycle Proteins D044842:Cullin Proteins D005786:Gene Expression Regulation D023281:Genomics D008297:Male D008540:Meiosis D051379:Mice D018345:Mice, Knockout D000070956:MutL Proteins D059372:Nucleotide Motifs D012708:Sertoli Cells D059010:Single-Cell Analysis D013091:Spermatogenesis D013737:Testis
single-cell testis gene regulation mouse genomics factor analysis computational biology genetics infertility meiosis systems biology