| First Author | Song EC | Year | 2023 |
| Journal | Cell Death Differ | Volume | 30 |
| Issue | 2 | Pages | 515-526 |
| PubMed ID | 36526896 | Mgi Jnum | J:340934 |
| Mgi Id | MGI:7439011 | Doi | 10.1038/s41418-022-01101-0 |
| Citation | Song EC, et al. (2023) DeltaNp63 maintains the fidelity of the myoepithelial cell lineage and directs cell differentiation programs in the murine salivary gland. Cell Death Differ 30(2):515-526 |
| abstractText | Salivary glands consist of several epithelial cell types of distinct lineages and functional characteristics that are established by directed differentiation programs of resident stem and progenitor cells. We have shown that DeltaNp63, a crucial transcriptional regulator of stem/progenitor cells, is enriched in both the basal and myoepithelial cell (MEC) populations and that DeltaNp63 positive cells maintain all the descendent epithelial cell lineages of the adult mouse salivary glands (mSGs). Although this pivotal role of DeltaNp63 in driving the broader epithelial cell fate and identity in the mSG has been demonstrated, how DeltaNp63 functions specifically in the commitment and differentiation of the MEC population is less understood. Using multiple genetic mouse models that allow for cell tracing, we show that DeltaNp63 is critical in maintaining and renewing MECs, in part through the transcriptional regulation of Acta2 gene expression, a defining marker of this cell population. We demonstrate that during adult mSG homeostasis, DeltaNp63 enriched MECs function as bipotent progenitor cells that maintain not only the MEC population, but also the distinctly different ductal cell lineages. The fidelity of this process is dependent on DeltaNp63 expression, since MEC-specific ablation of DeltaNp63 results in altered MEC differentiation and affects cellular plasticity resulting in aberrant differentiation of the intercalated ducts and acinar cells. In contrast, we find that the contribution of MECs to ductal and acinar cell regeneration following severe injury is independent of DeltaNp63. Our observations offer new insights into cellular mechanisms driving MEC fate choices and differentiation programs in the context of salivary gland homeostasis and in response to injury and regeneration. Long term, these findings have implications for better treatment of salivary gland dysfunction through stem cell-based approaches. |
