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Integrated single-cell transcriptomics and chromatin accessibility analysis reveals novel regulators of mammary epithelial cell identity

Nicholas Pervolarakis, Quy H. Nguyen, Guadalupe Gutierrez, Peng Sun, Darisha Jhutty, Grace XY Zheng, Corey M Nemec, Xing Dai, Kazuhide Watanabe, Kai Kessenbrock
doi: https://doi.org/10.1101/740746
Nicholas Pervolarakis
1Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697
2Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697
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Quy H. Nguyen
1Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697
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Guadalupe Gutierrez
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Peng Sun
1Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697
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Darisha Jhutty
310X Genomics; 7068 Koll Center Parkway, Suite 401, Pleasanton, CA 94566
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Grace XY Zheng
310X Genomics; 7068 Koll Center Parkway, Suite 401, Pleasanton, CA 94566
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Corey M Nemec
310X Genomics; 7068 Koll Center Parkway, Suite 401, Pleasanton, CA 94566
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Xing Dai
1Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697
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Kazuhide Watanabe
4RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
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  • For correspondence: kai.kessenbrock{at}uci.edu kazuhide.watanabe{at}riken.jp
Kai Kessenbrock
1Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697
2Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697
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  • For correspondence: kai.kessenbrock{at}uci.edu kazuhide.watanabe{at}riken.jp
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ABSTRACT

The mammary epithelial cell (MEC) system is a bi-layered ductal epithelial network consisting of luminal and basal cells, which is maintained by a lineage of stem and progenitor cell populations. Here, we used integrated single-cell transcriptomics and chromatin accessibility analysis to reconstruct the cell types of the mouse MEC system and their underlying gene regulatory features in an unbiased manner. We define previously unrealized differentiation states within the secretory type of luminal cells, which can be divided into distinct clusters of progenitor and mature secretory cells. By integrating single-cell transcriptomics and chromatin accessibility landscapes, we identified novel cis- and trans-regulatory elements that are differentially activated in the specific epithelial cell types and our newly defined luminal differentiation states. Our work provides an unprecedented resource to reveal novel cis/trans regulatory elements associated with MEC identity and differentiation that will serve as a valuable reference to determine how the chromatin accessibility landscape changes during breast cancer.

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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 August 20, 2019.
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Integrated single-cell transcriptomics and chromatin accessibility analysis reveals novel regulators of mammary epithelial cell identity
Nicholas Pervolarakis, Quy H. Nguyen, Guadalupe Gutierrez, Peng Sun, Darisha Jhutty, Grace XY Zheng, Corey M Nemec, Xing Dai, Kazuhide Watanabe, Kai Kessenbrock
bioRxiv 740746; doi: https://doi.org/10.1101/740746
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Integrated single-cell transcriptomics and chromatin accessibility analysis reveals novel regulators of mammary epithelial cell identity
Nicholas Pervolarakis, Quy H. Nguyen, Guadalupe Gutierrez, Peng Sun, Darisha Jhutty, Grace XY Zheng, Corey M Nemec, Xing Dai, Kazuhide Watanabe, Kai Kessenbrock
bioRxiv 740746; doi: https://doi.org/10.1101/740746

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