| First Author | Chatzeli L | Year | 2023 |
| Journal | Dev Cell | Volume | 58 |
| Issue | 2 | Pages | 94-109.e6 |
| PubMed ID | 36693323 | Mgi Jnum | J:333004 |
| Mgi Id | MGI:7432264 | Doi | 10.1016/j.devcel.2022.12.009 |
| Citation | Chatzeli L, et al. (2023) A cellular hierarchy of Notch and Kras signaling controls cell fate specification in the developing mouse salivary gland. Dev Cell 58(2):94-109.e6 |
| abstractText | The development of the mouse salivary gland involves a tip-driven process of branching morphogenesis that takes place in concert with differentiation into acinar, myoepithelial, and ductal (basal and luminal) sub-lineages. By combining clonal lineage tracing with a three-dimensional (3D) reconstruction of the branched epithelial network and single-cell RNA-seq analysis, we show that in tips, a heterogeneous population of renewing progenitors transition from a Krt14+ multipotent state to unipotent states via two transcriptionally distinct bipotent states, one restricted to the Krt14+ basal and myoepithelial lineage and the other to the Krt8+ acinar and luminal lineage. Using genetic perturbations, we show how the differential expression of Notch signaling correlates with spatial segregation, exits from multipotency, and promotes the Krt8+ lineage, whereas Kras activation promotes proacinar fate. These findings provide a mechanistic basis for how positional cues within growing tips regulate the process of lineage segregation and ductal patterning. |
