Progenitor/Stem Cell Function During Salivary Gland Development

Fibroblast growth factor signaling through FGFR2b, is critical for progenitor cell proliferation during fetal organogenesis in mice and humans. Salivary gland acinar cells are critical for saliva production and oral health, and the loss of functional acinar cells after irradiation for head and neck cancer is a major clinical challenge. However, the role of FGFR signaling in specific populations later in development and during acinar differentiation are unknown. We generated a single-cell RNA-seq analysis at multiple stages of murine salivary gland development, which provided an atlas of the transcriptional landscape during development. In order to investigate the role of FGFRs in salivary progenitor cell lineages and functions we used conditional deletion of murine FGFRs in vivo to identify essential roles for FGFRs in craniofacial, early SG development and progenitor function during duct homeostasis. Importantly, we discovered that FGFR2b, via MAPK signaling, was critical for seromucous acinar differentiation and secretory gene expression, while FGFR1b was dispensable. We showed that FGF7, expressed by myoepithelial cells, activates the FGFR2b-dependent seromucous transcriptional program. Thus, we proposed a model where myoepithelial-derived FGF7 drives seromucous acinar differentiation, providing a rationale for targeting FGFR2b signaling in regenerative therapies to restore acinar function.

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