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Article ; Online: Salivary gland function, development, and regeneration.

Chibly, Alejandro M / Aure, Marit H / Patel, Vaishali N / Hoffman, Matthew P

2022 Volume 102, Issue 3, Page(s) 1495–1552

Abstract: Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological function of salivary glands, as well as how they are affected by disease and injury, ... ...

Abstract	Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological function of salivary glands, as well as how they are affected by disease and injury, will direct the development of therapy to repair and regenerate them. Significant recent advances, particularly in the OMICS field, increase our understanding of how salivary glands develop at the cellular, molecular, and genetic levels: the signaling pathways involved, the dynamics of progenitor cell lineages in development, homeostasis, and regeneration, and the role of the extracellular matrix microenvironment. These provide a template for cell and gene therapies as well as bioengineering approaches to repair or regenerate salivary function.
MeSH term(s)	Cell Lineage ; Humans ; Oral Health ; Regeneration/physiology ; Salivary Glands/physiology ; Signal Transduction
Language	English
Publishing date	2022-03-28
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Intramural
ZDB-ID	209902-0
ISSN	1522-1210 ; 0031-9333
ISSN (online)	1522-1210
ISSN	0031-9333
DOI	10.1152/physrev.00015.2021
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Article: FGFR2b 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

Research square

2023

Abstract: Exocrine secretory 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, ... ...

Abstract	Exocrine secretory 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 epithelial SG populations later in development and during acinar differentiation are unknown. Here, we predicted FGFR dependence in specific populations using scRNAseq data and conditional mouse models to delete FGFRs in vivo. We identifed essential roles for FGFRs in craniofacial and early SG development, as well as progenitor function during duct homeostasis. Importantly, we discovered that FGFR2b was critical for seromucous and serous acinar cell differentiation and secretory gene expression (
Language	English
Publishing date	2023-02-16
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2557484/v1
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Article ; Online: 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

Nature communications

2023 Volume 14, Issue 1, Page(s) 6485

Abstract: 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. ... ...

Abstract	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.
MeSH term(s)	Animals ; Mice ; Cell Differentiation/genetics ; Homeostasis ; Orosomucoid ; Salivary Glands ; Signal Transduction
Chemical Substances	Orosomucoid ; Fgfr2 protein, mouse (EC 2.7.10.1)
Language	English
Publishing date	2023-10-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-42243-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Concise Review: A Critical Evaluation of Criteria Used to Define Salivary Gland Stem Cells.

Weng, Pei-Lun / Aure, Marit H / Ovitt, Catherine E

Stem cells (Dayton, Ohio)

2019 Volume 37, Issue 9, Page(s) 1144–1150

Abstract: In the effort to develop cell-based therapies to treat salivary gland dysfunction, many different populations of cells in the adult salivary glands have been proposed as stem cells. These cell populations vary, depending on the assay used, and are often ... ...

Abstract	In the effort to develop cell-based therapies to treat salivary gland dysfunction, many different populations of cells in the adult salivary glands have been proposed as stem cells. These cell populations vary, depending on the assay used, and are often nonoverlapping, leading to the conclusion that salivary glands harbor multiple stem cells. The goal of this review is to critically appraise the assays and properties used to identify stem cells in the adult salivary gland, and to consider the caveats of each. Re-evaluation of the defining criteria may help to reconcile the many potential stem cell populations described in the salivary gland, in order to increase comparability between studies and build consensus in the field. Stem Cells 2019;37:1144-1150.
MeSH term(s)	Adult ; Biomarkers/metabolism ; Cell Differentiation/physiology ; Cell Lineage/physiology ; Cell Proliferation/physiology ; Cell Self Renewal/physiology ; Humans ; Salivary Glands/cytology ; Salivary Glands/metabolism ; Stem Cell Transplantation/methods ; Stem Cells/cytology ; Stem Cells/metabolism ; Stem Cells/physiology
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-06-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1143556-2
ISSN	1549-4918 ; 1066-5099
ISSN (online)	1549-4918
ISSN	1066-5099
DOI	10.1002/stem.3046
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Article ; Online: Generation of a Single-Cell RNAseq Atlas of Murine Salivary Gland Development.

Hauser, Belinda R / Aure, Marit H / Kelly, Michael C / Hoffman, Matthew P / Chibly, Alejandro M

iScience

2020 Volume 23, Issue 12, Page(s) 101838

Abstract: Understanding the dynamic transcriptional landscape throughout organ development will provide a template for regenerative therapies. Here, we generated a single-cell RNA sequencing atlas of murine submandibular glands identifying transcriptional profiles ...

Abstract	Understanding the dynamic transcriptional landscape throughout organ development will provide a template for regenerative therapies. Here, we generated a single-cell RNA sequencing atlas of murine submandibular glands identifying transcriptional profiles that revealed cellular heterogeneity during landmark developmental events: end bud formation, branching morphogenesis, cytodifferentiation, maturation, and homeostasis. Trajectory inference analysis suggests plasticity among acinar and duct populations. We identify transcription factors correlated with acinar differentiation including
Language	English
Publishing date	2020-11-20
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2020.101838
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Neurotrophin signaling is a central mechanism of salivary dysfunction after irradiation that disrupts myoepithelial cells.

Chibly, Alejandro M / Patel, Vaishali N / Aure, Marit H / Pasquale, Mary C / Martin, Gemma E / Ghannam, Mousa / Andrade, Julianne / Denegre, Noah G / Simpson, Colleen / Goldstein, David P / Liu, Fei-Fei / Lombaert, Isabelle M A / Hoffman, Matthew P

NPJ Regenerative medicine

2023 Volume 8, Issue 1, Page(s) 17

Abstract: The mechanisms that prevent regeneration of irradiated (IR) salivary glands remain elusive. Bulk RNAseq of IR versus non-IR human salivary glands showed that neurotrophin signaling is highly disrupted post-radiation. Neurotrophin receptors (NTRs) were ... ...

Abstract	The mechanisms that prevent regeneration of irradiated (IR) salivary glands remain elusive. Bulk RNAseq of IR versus non-IR human salivary glands showed that neurotrophin signaling is highly disrupted post-radiation. Neurotrophin receptors (NTRs) were significantly upregulated in myoepithelial cells (MECs) post-IR, and single cell RNAseq revealed that MECs pericytes, and duct cells are the main sources of neurotrophin ligands. Using two ex vivo models, we show that nerve growth factor (NGF) induces expression of MEC genes during development, and upregulation of NTRs in adult MECs is associated with stress-induced plasticity and morphological abnormalities in IR human glands. As MECs are epithelial progenitors after gland damage and are required for proper acinar cell contraction and secretion, we propose that MEC-specific upregulation of NTRs post-IR disrupts MEC differentiation and potentially impedes the ability of the gland to regenerate.
Language	English
Publishing date	2023-03-25
Publishing country	United States
Document type	Journal Article
ISSN	2057-3995
ISSN (online)	2057-3995
DOI	10.1038/s41536-023-00290-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Limited Regeneration of Adult Salivary Glands after Severe Injury Involves Cellular Plasticity.

Weng, Pei-Lun / Aure, Marit H / Maruyama, Takamitsu / Ovitt, Catherine E

Cell reports

2018 Volume 24, Issue 6, Page(s) 1464–1470.e3

Abstract: In the adult salivary glands, the origin of replacement and regenerated acinar cells remains unclear. Although many reports describe the identification of stem cells in adult salivary glands, we have shown that differentiated acinar cells can be ... ...

Abstract	In the adult salivary glands, the origin of replacement and regenerated acinar cells remains unclear. Although many reports describe the identification of stem cells in adult salivary glands, we have shown that differentiated acinar cells can be maintained and regenerated through self-duplication. Here, we have used genetic mouse models to further investigate acinar cell replacement and regeneration during homeostasis and after injury. Under normal conditions or after duct ligation, replacement of duct and acinar cells occurs through lineage-restricted progenitors. In contrast, after irradiation, in vivo lineage tracing shows that acinar, as well as duct, cells contribute to acinar cell regeneration, revealing that cellular plasticity is involved in salivary gland repair. Our results also indicate that even after radiation damage, several cell populations have regenerative potential for restoring salivary gland function.
MeSH term(s)	Cell Differentiation ; Cell Plasticity/genetics ; Cell Proliferation ; Humans ; Salivary Glands/metabolism
Language	English
Publishing date	2018-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2018.07.016
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands.

Mauduit, Olivier / Aure, Marit H / Delcroix, Vanessa / Basova, Liana / Srivastava, Amrita / Umazume, Takeshi / Mays, Jacqueline W / Bellusci, Saverio / Tucker, Abigail S / Hajihosseini, Mohammad K / Hoffman, Matthew P / Makarenkova, Helen P

Cell reports

2022 Volume 39, Issue 2, Page(s) 110663

Abstract: Fibroblast growth factor 10 (FGF10) is well established as a mesenchyme-derived growth factor and a critical regulator of fetal organ development in mice and humans. Using a single-cell RNA sequencing (RNA-seq) atlas of salivary gland (SG) and a ... ...

Abstract	Fibroblast growth factor 10 (FGF10) is well established as a mesenchyme-derived growth factor and a critical regulator of fetal organ development in mice and humans. Using a single-cell RNA sequencing (RNA-seq) atlas of salivary gland (SG) and a tamoxifen inducible Fgf10
MeSH term(s)	Animals ; Epithelial Cells/metabolism ; Fibroblast Growth Factor 10/genetics ; Fibroblast Growth Factor 10/metabolism ; Forkhead Transcription Factors/metabolism ; Mice ; Receptor, Fibroblast Growth Factor, Type 2/genetics ; Receptor, Fibroblast Growth Factor, Type 2/metabolism ; Salivary Glands/cytology ; Salivary Glands/metabolism ; Signal Transduction
Chemical Substances	Fgf10 protein, mouse ; Fibroblast Growth Factor 10 ; Forkhead Transcription Factors ; Foxi1 protein, mouse ; Receptor, Fibroblast Growth Factor, Type 2 (EC 2.7.10.1)
Language	English
Publishing date	2022-04-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.110663
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Article ; Online: Neurotrophin signaling is a central mechanism of salivary dysfunction after irradiation that disrupts myoepithelial cells

Alejandro M. Chibly / Vaishali N. Patel / Marit H. Aure / Mary C. Pasquale / Gemma E. Martin / Mousa Ghannam / Julianne Andrade / Noah G. Denegre / Colleen Simpson / David P. Goldstein / Fei-Fei Liu / Isabelle M. A. Lombaert / Matthew P. Hoffman

npj Regenerative Medicine, Vol 8, Iss 1, Pp 1-

2023 Volume 16

Abstract: Abstract The mechanisms that prevent regeneration of irradiated (IR) salivary glands remain elusive. Bulk RNAseq of IR versus non-IR human salivary glands showed that neurotrophin signaling is highly disrupted post-radiation. Neurotrophin receptors (NTRs) ...

Abstract	Abstract The mechanisms that prevent regeneration of irradiated (IR) salivary glands remain elusive. Bulk RNAseq of IR versus non-IR human salivary glands showed that neurotrophin signaling is highly disrupted post-radiation. Neurotrophin receptors (NTRs) were significantly upregulated in myoepithelial cells (MECs) post-IR, and single cell RNAseq revealed that MECs pericytes, and duct cells are the main sources of neurotrophin ligands. Using two ex vivo models, we show that nerve growth factor (NGF) induces expression of MEC genes during development, and upregulation of NTRs in adult MECs is associated with stress-induced plasticity and morphological abnormalities in IR human glands. As MECs are epithelial progenitors after gland damage and are required for proper acinar cell contraction and secretion, we propose that MEC-specific upregulation of NTRs post-IR disrupts MEC differentiation and potentially impedes the ability of the gland to regenerate.
Keywords	Medicine ; R
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Salivary gland homeostasis is maintained through acinar cell self-duplication.

Aure, Marit H / Konieczny, Stephen F / Ovitt, Catherine E

Developmental cell

2015 Volume 33, Issue 2, Page(s) 231–237

Abstract: Current dogma suggests that salivary gland homeostasis is stem cell dependent. However, the extent of stem cell contribution to salivary gland maintenance has not been determined. We investigated acinar cell replacement during homeostasis, growth, and ... ...

Abstract	Current dogma suggests that salivary gland homeostasis is stem cell dependent. However, the extent of stem cell contribution to salivary gland maintenance has not been determined. We investigated acinar cell replacement during homeostasis, growth, and regeneration, using an inducible CreER(T2) expressed under the control of the Mist1 gene locus. Genetic labeling, followed by a chase period, showed that acinar cell replacement is not driven by the differentiation of unlabeled stem cells. Analysis using R26(Brainbow2.1) reporter revealed continued proliferation and clonal expansion of terminally differentiated acinar cells in all major salivary glands. Induced injury also demonstrated the regenerative potential of pre-labeled acinar cells. Our results support a revised model for salivary gland homeostasis based predominantly on self-duplication of acinar cells, rather than on differentiation of stem cells. The proliferative capacity of differentiated acinar cells may prove critical in the implementation of cell-based strategies to restore the salivary glands.
MeSH term(s)	Acinar Cells/cytology ; Acinar Cells/metabolism ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cell Differentiation/genetics ; Cell Proliferation ; Homeostasis/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Salivary Glands/cytology ; Salivary Glands/physiology ; Stem Cells/cytology
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Bhlha15 protein, mouse
Language	English
Publishing date	2015-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2015.02.013
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Zs.A 5742: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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