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Single-cell chromatin accessibility of developing murine pancreas identifies cell state-specific gene regulatory programs

View ORCID ProfileSean de la O, Zhe Liu, View ORCID ProfileSean Chang, View ORCID ProfileJulie B. Sneddon
doi: https://doi.org/10.1101/2022.10.01.510484
Sean de la O
1Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA
2Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA
3Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA
4Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
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  • ORCID record for Sean de la O
Zhe Liu
1Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA
2Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA
3Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA
4Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
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Sean Chang
1Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA
2Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA
3Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA
4Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
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Julie B. Sneddon
1Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA
2Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA
3Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA
4Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
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  • For correspondence: julie.sneddon@ucsf.edu
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Abstract

Numerous studies have characterized the existence of cell subtypes, along with their corresponding transcriptional profiles, within the developing mouse pancreas. The upstream mechanisms that initiate and maintain gene expression programs across cell states, however, remain largely unknown. Here, we generate single-nucleus ATAC-Sequencing data of developing murine pancreas and perform an integrated, multi-omic analysis of both chromatin accessibility and RNA expression to describe the chromatin landscape of both the developing epithelium and mesenchyme at E14.5 at single-cell resolution. We identify candidate transcription factors regulating cell fate and construct gene regulatory networks of active transcription factor binding to regulatory regions of downstream target genes. This work serves as a valuable resource for the field of pancreatic biology in general and contributes to our understanding of lineage plasticity among endocrine cell types. In addition, these data identify which epigenetic states should be represented in the differentiation of stem cells to the pancreatic beta cell fate in order to best recapitulate in vitro the gene regulatory networks that are critical for progression along the beta cell lineage in vivo.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 02, 2022.
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Single-cell chromatin accessibility of developing murine pancreas identifies cell state-specific gene regulatory programs
Sean de la O, Zhe Liu, Sean Chang, Julie B. Sneddon
bioRxiv 2022.10.01.510484; doi: https://doi.org/10.1101/2022.10.01.510484
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Single-cell chromatin accessibility of developing murine pancreas identifies cell state-specific gene regulatory programs
Sean de la O, Zhe Liu, Sean Chang, Julie B. Sneddon
bioRxiv 2022.10.01.510484; doi: https://doi.org/10.1101/2022.10.01.510484

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