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.
Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Cell Rep. 2020 Oct 20;33(3):108273. doi: 10.1016/j.celrep.2020.108273.
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.
乳腺上皮细胞 (MEC) 系统是由腔细胞和基底细胞组成的双层导管上皮，由一系列干细胞和祖细胞群体维持。在这里，我们使用整合的单细胞转录组学和染色质可及性分析，以无偏倚的方式重建小鼠 MEC 系统的细胞类型及其潜在的基因调控特征。我们定义了分泌型腔细胞中的分化状态，这些细胞形成了一个连续的普通腔前体细胞和泌乳祖细胞的谱系。通过整合单细胞转录组学和染色质可及性图谱，我们鉴定了在特定上皮细胞类型和我们新定义的腔细胞分化状态中差异激活的顺式和反式调控元件。我们的工作提供了一个资源，以揭示与 MEC 身份和分化相关的顺式/反式调控元件，这将作为一个参考，以确定染色质可及性图谱在乳腺癌发生过程中如何变化。
