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

39 Pages Posted: 29 Aug 2019 Publication Status: Review Complete

See all articles by Nicholas Pervolarakis

Nicholas Pervolarakis

University of California, Irvine - Department of Biological Chemistry

Peng Sun

University of California, Irvine - Department of Biological Chemistry

Guadalupe Gutierrez

University of California, Irvine - Department of Biological Chemistry

Quy H. Nguyen

University of California, Irvine - Department of Biological Chemistry

Darisha Jhutty

10X Genomics

Grace XY Zheng

10X Genomics

Corey M. Nemec

10X Genomics

Xing Dai

University of California, Irvine - Department of Biological Chemistry

Kazuhide Watanabe

RIKEN Center for Integrative Medical Sciences

Kai Kessenbrock

University of California, Irvine - Department of Biological Chemistry; University of California, Irvine - Center for Complex Biological Systems

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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 basal and luminal 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 framework 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.

Keywords: Mammary stem cells, single-cell RNAseq, single-cell ATACseq, chromatin accessibility, cellular heterogeneity, normal homeostasis, breast cancer

Suggested Citation

Pervolarakis, Nicholas and Sun, Peng and Gutierrez, Guadalupe and Nguyen, Quy H. and Jhutty, Darisha and XY Zheng, Grace and Nemec, Corey M. and Dai, Xing and Watanabe, Kazuhide and Kessenbrock, Kai, Integrated Single-Cell Transcriptomics and Chromatin Accessibility Analysis Reveals Novel Regulators of Mammary Epithelial Cell Identity (August 27, 2019). Available at SSRN: https://ssrn.com/abstract=3443688 or http://dx.doi.org/10.2139/ssrn.3443688
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Nicholas Pervolarakis

University of California, Irvine - Department of Biological Chemistry

Irvine, CA 92697
United States

Peng Sun

University of California, Irvine - Department of Biological Chemistry

Irvine, CA 92697
United States

Guadalupe Gutierrez

University of California, Irvine - Department of Biological Chemistry

Irvine, CA 92697
United States

Quy H. Nguyen

University of California, Irvine - Department of Biological Chemistry

Irvine, CA 92697
United States

Darisha Jhutty

10X Genomics

7068 Koll Center Parkway, Suite 401,
Pleasanton, CA 94566
United States

Grace XY Zheng

10X Genomics

7068 Koll Center Parkway, Suite 401,
Pleasanton, CA 94566
United States

Corey M. Nemec

10X Genomics

7068 Koll Center Parkway, Suite 401,
Pleasanton, CA 94566
United States

Xing Dai

University of California, Irvine - Department of Biological Chemistry

Irvine, CA 92697
United States

Kazuhide Watanabe

RIKEN Center for Integrative Medical Sciences ( email )

1-7-22, Suehiro-cho
Tsurumi-ku
Yokohama, Kanagawa
Japan

Kai Kessenbrock (Contact Author)

University of California, Irvine - Department of Biological Chemistry ( email )

Irvine, CA 92697
United States

University of California, Irvine - Center for Complex Biological Systems ( email )

Irvine, CA 92697
United States

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