FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation.
FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation.
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DOI：
10.1038/s41467-023-42243-0
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发表时间：
2023-10-14
影响因子：
16.6
通讯作者：
Hoffman, Matthew P.
中科院分区：
文献类型：
--
作者：
Aure, Marit H.;Symonds, Jennifer M.;Villapudua, Carlos U.;Dodge, Joshua T.;Werner, Sabine;Knosp, Wendy M.;Hoffman, Matthew P.
唾液腺（SG）外分泌腺泡细胞对口腔健康至关重要，功能性腺泡细胞的丧失是一个主要的临床挑战。成纤维细胞生长因子受体（FGFR）对包括SG在内的多个器官的早期发育至关重要。然而，FGFR信号传导在发育后期和腺泡分化期间的特定群体中的作用尚不清楚。在这里，我们使用scRNAseq和小鼠FGFR的条件性缺失在体内，以确定在颅面，早期SG发展和导管稳态过程中的祖细胞功能的FGFR的重要作用。重要的是，我们还发现，FGFR 2通过MAPK信号传导对浆液粘液腺泡分化和分泌基因表达至关重要，而FGFR 1则不起作用。我们表明，FGF 7，肌上皮细胞（MEC）表达，激活FGFR 2依赖的血清粘液转录程序。在这里，我们提出了一个模型，MEC衍生的FGF 7驱动血清粘液腺泡分化，提供了一个基本原理，在再生疗法中靶向FGFR 2信号，以恢复腺泡功能。腺体损伤后恢复唾液腺泡细胞是一个重大的临床挑战。在这里，作者确定了FGF 7-FGFR 2-MAPK信号作为再生靶点，对调节浆液粘液腺泡分化的肌上皮-腺泡串扰至关重要。
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. Restoring salivary acinar cells after gland damage is a major clinical challenge. Here, authors identify FGF7-FGFR2-MAPK signaling as a regenerative target, critical for myoepithelial-acinar crosstalk that regulates seromucous acinar differentiation.
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影响因子：
4.6
作者：
Gao, Xin;Oei, Maria S.;Melvin, James E.
通讯作者：
Melvin, James E.
影响因子：
13.6
作者：
通讯作者：
--
影响因子：
--
作者：
Choi JS;Shin HS;An HY;Kim YM;Lim JY
通讯作者：
Lim JY
影响因子：
3.2
作者：
Larsen, Helga S.;Aure, Marit H.;Peters, Sarah B.;Larsen, Melinda;Messelt, Edward B.;Galtung, Hilde Kanli
通讯作者：
Galtung, Hilde Kanli
影响因子：
5.8
作者：
Hauser BR;Aure MH;Kelly MC;Genomics and Computational Biology Core;Hoffman MP;Chibly AM
通讯作者：
Chibly AM