Integrated Single-Cell Transcriptomics and Chromatin Accessibility Analysis Reveals Regulators of Mammary Epithelial Cell Identity

Nicholas Pervolarakis; Quy H. Nguyen; Justice Williams; Yanwen Gong; Guadalupe Gutierrez; Peng Sun; Darisha Jhutty; Grace X.Y. Zheng; Corey M. Nemec; Xing Dai; Kazuhide Watanabe; Kai Kessenbrock

Cell Reports (Oct 2020)

Integrated Single-Cell Transcriptomics and Chromatin Accessibility Analysis Reveals Regulators of Mammary Epithelial Cell Identity

Nicholas Pervolarakis,
Quy H. Nguyen,
Justice Williams,
Yanwen Gong,
Guadalupe Gutierrez,
Peng Sun,
Darisha Jhutty,
Grace X.Y. Zheng,
Corey M. Nemec,
Xing Dai,
Kazuhide Watanabe,
Kai Kessenbrock

Affiliations

Nicholas Pervolarakis: Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA
Quy H. Nguyen: Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA
Justice Williams: Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA
Yanwen Gong: Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA
Guadalupe Gutierrez: Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA
Peng Sun: Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA
Darisha Jhutty: 10X Genomics, 7068 Koll Center Parkway, Suite 401, Pleasanton, CA 94566, USA
Grace X.Y. Zheng: 10X Genomics, 7068 Koll Center Parkway, Suite 401, Pleasanton, CA 94566, USA
Corey M. Nemec: 10X Genomics, 7068 Koll Center Parkway, Suite 401, Pleasanton, CA 94566, USA
Xing Dai: Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA
Kazuhide Watanabe: RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Corresponding author
Kai Kessenbrock: Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA; Corresponding author

Journal volume & issue: Vol. 33, no. 3
p. 108273

Abstract

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Summary: The mammary epithelial cell (MEC) system is a bilayered ductal epithelium of luminal and basal cells, maintained by a lineage of stem and progenitor 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 differentiation states within the secretory type of luminal cells, which forms a continuous spectrum of general luminal progenitor and lactation-committed progenitor cells. By integrating single-cell transcriptomics and chromatin accessibility landscapes, we identify 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 a resource to reveal cis/trans-regulatory elements associated with MEC identity and differentiation that will serve as a reference to determine how the chromatin accessibility landscape changes during breast cancer.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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