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FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation

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 specifi...

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Autores principales: Aure, Marit H., Symonds, Jennifer M., Villapudua, Carlos U., Dodge, Joshua T., Werner, Sabine, Knosp, Wendy M., Hoffman, Matthew P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576811/
https://www.ncbi.nlm.nih.gov/pubmed/37838739
http://dx.doi.org/10.1038/s41467-023-42243-0
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author Aure, Marit H.
Symonds, Jennifer M.
Villapudua, Carlos U.
Dodge, Joshua T.
Werner, Sabine
Knosp, Wendy M.
Hoffman, Matthew P.
author_facet Aure, Marit H.
Symonds, Jennifer M.
Villapudua, Carlos U.
Dodge, Joshua T.
Werner, Sabine
Knosp, Wendy M.
Hoffman, Matthew P.
author_sort Aure, Marit H.
collection PubMed
description 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.
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spelling pubmed-105768112023-10-16 FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation Aure, Marit H. Symonds, Jennifer M. Villapudua, Carlos U. Dodge, Joshua T. Werner, Sabine Knosp, Wendy M. Hoffman, Matthew P. Nat Commun Article 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. Nature Publishing Group UK 2023-10-14 /pmc/articles/PMC10576811/ /pubmed/37838739 http://dx.doi.org/10.1038/s41467-023-42243-0 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Aure, Marit H.
Symonds, Jennifer M.
Villapudua, Carlos U.
Dodge, Joshua T.
Werner, Sabine
Knosp, Wendy M.
Hoffman, Matthew P.
FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title_full FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title_fullStr FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title_full_unstemmed FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title_short FGFR2 is essential for salivary gland duct homeostasis and MAPK-dependent seromucous acinar cell differentiation
title_sort fgfr2 is essential for salivary gland duct homeostasis and mapk-dependent seromucous acinar cell differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10576811/
https://www.ncbi.nlm.nih.gov/pubmed/37838739
http://dx.doi.org/10.1038/s41467-023-42243-0
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