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
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.
