Abstract
Purpose :
Myoepithelial cells (MECs) are a unique subset of epithelial cells that possess several smooth muscle cell characteristics, such as a high number of actin-myosin filaments and the ability to contract. So far, no comparative analysis of MECs in different exocrine glands had ever evaluated their differences.
Methods :
We analyzed various publicly available scRNAseq data from mouse exocrine glands to identify MECs shared and unique characteristics. We mined scRNAseq dataset for tissues displaying a secretory function: submandibular gland (GSE175649 and GSE150327), mammary gland (Tabula Muris), and our LG dataset (GSE232146). All of these datasets were integrated together using the reciprocal PCA (RPCA) method. Then, Uniform Manifold Approximation and Projection (UMAP) algorithm was used for dimensionality reduction and visualization. Pathway enrichment analysis was conducted using Metascape. Expression of genes and cell-cell interactions were validated by lineage tracing and immunostaining followed by confocal microscopy.
Results :
Following unsupervised clustering, we identified a cluster labeled by Acta2 and Epcam, consistent with MEC identity. The most significant processes were related to cell motility and cytoskeleton dynamics, namely “supramolecular fiber organization” and “positive regulation of cell migration”. The most conserved MECs markers across tissues (FC>1.5, expressed by at least 70% of MECs from each gland) were considered as a universal MEC signature. MECs also expressed cytokeratin Krt14, the regulator of ion pumps and channels Fxyd3, the lipid carrier Apoe, the smooth muscle marker Csrp1, the modulator of myogenic differentiation Igfbp5, and surprisingly, some immunoregulators: cathepsin-L (Ctsl) and the antiviral protein interferon-induced transmembrane protein-3 (Ifitm3). Consistent with our previous findings MECs in all three glands expressed genes involved in cellular plasticity. MECs and signals to Kit+ epithelial progenitors-like cells of the ducts Moreover, MECs interact with many non-epithelial cell types such as myeloid cells, fibroblast, and endothelial cells.
Conclusions :
In summary, genes related to the contractile function of MECs are highly conserved across all three tissues. However, our study suggests that MEC plasticity and regenerative potential could vary, influenced by the specific tissue context to which they belong.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.