Project description:The mammary epithelial cell (MEC) system is a bi-layered ductal epithelial network consisting of luminal and basal cells, maintained by a lineage of 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 differentiation states within the secretory type of luminal cells, which can be defined as a continuous spectrum of progenitor and mature secretory cells. By integrating single-cell transcriptomics and chromatin accessibility landscapes, we identified 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 resource to reveal 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.
Project description:The mammary epithelial cell (MEC) system is a bi-layered ductal epithelial network consisting of luminal and basal cells, maintained by a lineage of 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 differentiation states within the secretory type of luminal cells, which can be defined as a continuous spectrum of progenitor and mature secretory cells. By integrating single-cell transcriptomics and chromatin accessibility landscapes, we identified 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 resource to reveal 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.
Project description:The mammary gland is a unique organ as it undergoes most of its development during puberty and adulthood. Characterising the hierarchy of the various mammary epithelial cells and how they are regulated in response to gestation, lactation and involution is important for understanding how breast cancer develops. Recent studies have used numerous markers to enrich, isolate and characterise the different epithelial cell compartments within the adult mammary gland. However, in all of these studies only a handful of markers were used to define and trace cell populations. Therefore, there is a need for an unbiased and comprehensive description of mammary epithelial cells within the gland at different developmental stages. To this end we used single cell RNA sequencing (scRNAseq) to determine the gene expression profile of individual mammary epithelial cells across four adult developmental stages; nulliparous, mid gestation, lactation and post weaning (full natural involution). Our data from 25,010 individual cells identifies 8 distinct mammary epithelial cell populations and allows their hierarchical structure across development to be charted. Interestingly, the effect of gestation and lactation appeared to be more pronounced for some cell types. For example, our analysis revealed a cluster of luminal progenitor cells in post involution glands, which is distinct from progenitors found in nulliparous glands. The data also showed that few clusters could be fully characterized by a single marker gene. We argue instead that the epithelial cells – especially in the luminal compartment – should rather be conceptualized as being part of a continuous spectrum of differentiation. This view highlights the plasticity of the tissue and might help to explain some of the conflicting results from lineage tracing studies.