TY - JOUR
T1 - Unified single-cell analysis of testis gene regulation and pathology in five mouse strains
AU - Jung, Min
AU - Wells, Daniel
AU - Rusch, Jannette
AU - Ahmad, Suhaira
AU - Marchini, Jonathan
AU - Myers, Simon R.
AU - Conrad, Donald F.
N1 - Funding Information:
We thank Abul Usmani for assistance with mouse husbandry and advice on Pou5f1:GFP reporter ani- mals, Jeffrey Milbrandt and the WashU Genetics Department Single Cell Program for support, Liang Ma for providing Cul4a-/- mice, Joe Dougherty for providing Cnp mice, and Katinka Vigh-Conrad for assistance with figures. We also thank the Alvin J Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, MO, for the use of the High-Speed Cell Sorter Core, which provided cell sorting service. The Siteman Cancer Center is supported in part by an NCI Cancer Center Support Grant #P30 CA91842. This work was supported by National Institutes of Health Grants R01HD078641 and R01MH101810 to DFC, and Wellcome Trust grants 098387/Z/ 12/Z and 212284/Z/18/Z to SM and 109109/Z/15/Z to DW. Research reported in this publication was supported by the Office of the Director, of the National Institutes of Health under Award Number P51OD011092 to the Oregon National Primate Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
We thank Abul Usmani for assistance with mouse husbandry and advice on Pou5f1:GFP reporter animals, Jeffrey Milbrandt and the WashU Genetics Department Single Cell Program for support, Liang Ma for providing Cul4a-/- mice, Joe Dougherty for providing Cnp mice, and Katinka Vigh-Conrad for assistance with figures. We also thank the Alvin J Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, MO, for the use of the High-Speed Cell Sorter Core, which provided cell sorting service. The Siteman Cancer Center is supported in part by an NCI Cancer Center Support Grant #P30 CA91842. This work was supported by National Institutes of Health Grants R01HD078641 and R01MH101810 to DFC, and Wellcome Trust grants 098387/Z/ 12/Z and 212284/Z/18/Z to SM and 109109/Z/15/Z to DW. Research reported in this publication was supported by the Office of the Director, of the National Institutes of Health under Award Number P51OD011092 to the Oregon National Primate Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© Jung et al.
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.43966.001
DO - 10.7554/eLife.43966.001
M3 - Article
C2 - 31237565
AN - SCOPUS:85069296795
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e43966
ER -