Integrated Single-Cell Transcriptomics and Chromatin Accessibility Analysis Reveals Novel Regulators of Mammary Epithelial Cell Identity
39 Pages Posted: 29 Aug 2019 Sneak Peek Status: Review CompleteMore...
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
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