Unified single-cell analysis of testis gene regulation and pathology in five mouse strains.
Min JungDaniel WellsJannette RuschSuhaira AhmadJonathan MarchiniSimon R MyersDonald F ConradPublished in: eLife (2019)
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.
Keyphrases
- wild type
- single cell
- rna seq
- gene expression
- high throughput
- electronic health record
- induced apoptosis
- big data
- escherichia coli
- type diabetes
- public health
- genome wide
- high fat diet induced
- oxidative stress
- cell therapy
- metabolic syndrome
- cell death
- mesenchymal stem cells
- data analysis
- circulating tumor
- cell free
- risk assessment
- skeletal muscle
- machine learning
- bioinformatics analysis