A panel of Diversity Outbred mouse embryonic stem cells: enabling the functional characterization of natural genetic variation in vitro
- 1Mammalian Genetics, The Jackson Laboratory, Bar Harbor, ME, USA; Graduate School of Biomedical Sciences, Tufts University, Boston, MA, USA
Abstract
Phenotypic variation in pluripotent stem cells arises largely from genetic variants that impact stability of the pluripotent state, response to differentiation cues, and cell fate diversification. Panels derived from genetic reference populations leverage genetic diversity to map the loci influencing these molecular and cellular traits. Here we describe the first publicly available resource for in vitro systems genetics in Mus musculus: 299 genetically diverse, highly heterozygous embryonic stem cell lines derived from Diversity Outbred mice, with minimal kinship across the panel. We characterize genomic integrity and allelic variation across the panel and describe differences in pluripotency and differentiation networks in embryoid bodies. Mapping the genetic determinants of gene expression differences in response to cadmium exposure in embryoid bodies identified 13 regulatory hotspots, the largest acting on ribosome biogenesis genes. This panel enables mapping of loci and gene-by-environment interactions that influence molecular identity in pluripotent cells and their derived cell types.
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BibTeX
@misc{brady2026panel,
title = {{A panel of Diversity Outbred mouse embryonic stem cells: enabling the functional characterization of natural genetic variation in vitro}},
author = {M. M. Brady and E. Swanzey and K. Janeczko and S. J. Widmayer and H. B. Dewey and S. Aydin and W. Martin and C. Brunton and A. Srivastava and D. M. Gatti and L. G. Reinholdt and S. C. Munger and C. L. Baker},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.747888},
url = {https://www.biorxiv.org/content/10.64898/2026.09.11.747888v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A panel of Diversity Outbred mouse embryonic stem cells: enabling the functional characterization of natural genetic variation in vitro
AU - M. M. Brady
AU - E. Swanzey
AU - K. Janeczko
AU - S. J. Widmayer
AU - H. B. Dewey
AU - S. Aydin
AU - W. Martin
AU - C. Brunton
AU - A. Srivastava
AU - D. M. Gatti
AU - L. G. Reinholdt
AU - S. C. Munger
AU - C. L. Baker
PY - 2026
DA - 2026/09/11
PB - bioRxiv
DO - 10.64898/2026.09.11.747888
UR - https://www.biorxiv.org/content/10.64898/2026.09.11.747888v1
AB - Phenotypic variation in pluripotent stem cells arises largely from genetic variants that impact stability of the pluripotent state, response to differentiation cues, and cell fate diversification. Panels derived from genetic reference populations leverage genetic diversity to map the loci influencing these molecular and cellular traits. Here we describe the first publicly available resource for in vitro systems genetics in Mus musculus: 299 genetically diverse, highly heterozygous embryonic stem cell lines derived from Diversity Outbred mice, with minimal kinship across the panel. We characterize genomic integrity and allelic variation across the panel and describe differences in pluripotency and differentiation networks in embryoid bodies. Mapping the genetic determinants of gene expression differences in response to cadmium exposure in embryoid bodies identified 13 regulatory hotspots, the largest acting on ribosome biogenesis genes. This panel enables mapping of loci and gene-by-environment interactions that influence molecular identity in pluripotent cells and their derived cell types.
ER -