Exocrine acinar cells in salivary glands (SG) are critical for oral health and loss of functional acinar cells is a major clinical challenge. Fibroblast growth factor receptors (FGFR) are essential for early development of multiple organs, including SG. However, the role of FGFR signaling in specific populations later in development and during acinar differentiation are unknown. Here, we use scRNAseq and 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 also discover that FGFR2 via MAPK signaling is critical for seromucous acinar differentiation and secretory gene expression, while FGFR1 is dispensable. We show that FGF7, expressed by myoepithelial cells (MEC), activates the FGFR2-dependent seromucous transcriptional program. Here, we propose a model where MEC-derived FGF7 drives seromucous acinar differentiation, providing a rationale for targeting FGFR2 signaling in regenerative therapies to restore acinar function.

唾液腺 (SG) 中的外分泌腺泡细胞对于口腔健康至关重要，功能性腺泡细胞的丧失是一项重大的临床挑战。成纤维细胞生长因子受体 (FGFR) 对于包括 SG 在内的多个器官的早期发育至关重要。然而，FGFR 信号在特定群体发育后期和腺泡分化过程中的作用尚不清楚。在这里，我们使用 scRNAseq 和体内小鼠 FGFR 的条件删除来确定 FGFR 在颅面、早期 SG 发育和导管稳态过程中祖细胞功能中的重要作用。重要的是，我们还发现 FGFR2 通过 MAPK 信号传导对于浆液粘液腺泡分化和分泌基因表达至关重要，而 FGFR1 是可有可无的。我们发现，肌上皮细胞 (MEC) 表达的 FGF7 可激活 FGFR2 依赖性浆液粘液转录程序。在这里，我们提出了一个模型，其中 MEC 衍生的 FGF7 驱动浆液粘膜腺泡分化，为再生疗法中靶向 FGFR2 信号传导以恢复腺泡功能提供了理论基础。