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

综合单细胞转录组学和染色质可及性分析揭示乳腺上皮细胞身份的调节因子

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作者: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

Abstract

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.

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