A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary gland
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ABSTRACT:
PROVIDER: PRJNA780584 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16952890.fastq.gz | Fastqsanger.gz | |||
| SRR16952891.fastq.gz | Fastqsanger.gz | |||
| SRR16952892.fastq.gz | Fastqsanger.gz | |||
| SRR16952893.fastq.gz | Fastqsanger.gz |
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Project description:Salivary glands are essential structures that secrete saliva to the oral cavity and maintain oral health. Development of salivary glands in mice and humans is controlled by mesenchymally expressed fibroblast growth factor-10 (FGF10). Using single cell RNA-seq atlas of the salivary gland and a tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5), but after P7, there is a switch in expression and only epithelial FGF10pos cells are observed after P15. Further RNAseq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos populations express the hallmark of ancient ionocyte signature Foxi1, Foxi2, Ascl3 and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10pos cells are specialized salivary gland ionocytes that are important for the ionic modification of saliva. In addition, they maintain FGF10-dependent glands homeostasis via communication with FGFR2b-expressing epithelial progenitor and myoepithelial cells
2022-04-12 | GSE188904 | GEO
Project description: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 Fgf10CreERT2:R26-tdTomato mouse, we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5) but, after P7, there is a switch in expression and only epithelial FGF10pos cells are observed after P15. Further RNA-seq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos population express the hallmarks of ancient ionocyte signature Forkhead box i1 and 2 (Foxi1, Foxi2), Achaete-scute homolog 3 (Ascl3), and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10pos cells are specialized SG ionocytes located in ducts and important for the ionic modification of saliva. In addition, they maintain FGF10-dependent gland homeostasis via communication with FGFR2bpos ductal and myoepithelial cells.
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Project description:Salivary glands produce saliva and play essential roles in digestion and oral health. Pluripotent stem cell-derived (PSC) organoids provide a powerful platform for studying salivary gland development and developing new regenerative therapy. The previous protocol of PSC-derived salivary gland organoids required complicated manufacturing processes, which hampered the organoids for basic research and clinical application.Here, by mimicking the regulatory mechanism of developing salivary glands, we reported the differentiation of induced embryonic salivary glands (iE-SGs) from mouse embryonic stem cells by step-wise treatment of retinoic acid and FGF10. We showed that the iE-SGs recapitulated early morphogenetic events, including the thickening and invagination of the salivary gland placode, and then formed initial buds. The iE-SGs also differentiated into developing ducts structures and could develop to striated and excretory ducts when transplanted in vivo. RNA- seq revealed that iE-SGs had gene expression profiles similar to mouse embryonic SMGs. Thus, our study provided an easy and safe method to generate iE-SGs and offered possibilities for studying events during salivary gland morphogenesis in vitro
2022-08-03 | GSE198489 | GEO
Project description:Transcriptional profiling of mouse 4-8 somite microdissected otic placodes from Fgf3/Fgf10 double heterozygotes (controls) compared to Fgf3/Fgf10 double null mutants. The purpose was to determine the effectors that are induced (or repressed) by Fgf3 and Fgf10 in the course of otic placode induction. Two condition experiment, double heterozygote vs. double null placodes. Biological replicas: 3 Fgf3+/-;Fgf10+/- and 3 Fgf3-/-;Fgf10-/- pools of ten placodes each.
2010-03-07 | E-GEOD-18702 | biostudies-arrayexpress
Project description:Transcriptional profiling of mouse 4-8 somite microdissected otic placodes from Fgf3/Fgf10 double heterozygotes (controls) compared to Fgf3/Fgf10 double null mutants. The purpose was to determine the effectors that are induced (or repressed) by Fgf3 and Fgf10 in the course of otic placode induction.
2010-03-01 | GSE18702 | GEO
Project description:Our previous data obtained by using immunohistochemistry showed, that Fgf10+/- (50% Fgf10 expression compared to WT) in hyperoxic condition at postnatal day 3 (P3) compared to WT has less vessel count in the lung and less muscularization of small capillaries in the lung. Furthermore, Fgf10+/- showed a drastic increase in mortality upon hyperoxic lung injury. Main question to be answer by this experiment is as followed: Does Fgf10+/- mice in normoxia from P0-P3 show different expression profiles at P3 compared to WT? To adress this question we harvest lungs at P3 from WT and Fgf10+/- . For this the mice were sacrificed by Ketamin/ Dormitor ip, lungs were perfused transcardiac with PBS and directly frozen in liquid nitrogen.
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Project description:Retinoic acid and FGF10 promote the differentiation of mESCs into induced embryonic salivary glands
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Project description:Our previous data obtained by using immunohistochemistry showed, that Fgf10+/- (50% Fgf10 expression compared to WT) in hyperoxic condition at postnatal day 3 (P3) compared to WT has less vessel count in the lung and less muscularization of small capillaries in the lung. Furthermore, Fgf10+/- showed a drastic increase in mortality upon hyperoxic lung injury. Main question to be answer by this experiment is as followed: Does Fgf10+/- mice after hyperoxia from P0-P3 show different expression profiles at P3 compared to WT? To adress this question we harvest lungs at P3 from WT and Fgf10+/- after hyperoxia treatment from P0-P3. For this the mice were sacrificed by Ketamin/ Dormitor ip, lungs were perfused transcardiac with PBS and directly frozen in liquid nitrogen.
2019-05-01 | GSE113102 | GEO
Project description:Our previous data obtained by using immunohistochemistry showed, that Fgf10+/- (50% Fgf10 expression compared to WT) in hyperoxic condition at postnatal day 3 (P3) compared to WT has less vessel count in the lung and less muscularization of small capillaries in the lung. Furthermore, Fgf10+/- showed a drastic increase in mortality upon hyperoxic lung injury. Main question to be answer by this experiment is as followed: Does Fgf10+/- mice after hyperoxia from P0-P3 show different expression profiles at P3 compared to WT? To adress this question we harvest lungs at P3 from WT and Fgf10+/- after hyperoxia treatment from P0-P3. For this the mice were sacrificed by Ketamin/ Dormitor ip, lungs were perfused transcardiac with PBS and directly frozen in liquid nitrogen.
2016-12-31 | GSE76301 | GEO
Project description:Xerostomia, or chronic dry mouth, is a common syndrome caused by a lack of saliva that can lead to severe eating difficulties, dental caries and oral candida infections. The prevalence of xerostomia increases with age and affects approximately 30% of people aged 65 or older. Given the large numbers of sufferers, and the potential increase in incidence given our aging population, it is important to understand the complex mechanisms that drive hyposalivation and the consequences for the dentition and oral mucosa. From this study we propose the Fgf10 +/- mouse as a model to investigate xerostomia. By following embryonic salivary gland development, in vivo and in vitro, we show that a reduction in Fgf10 causes a delay in branching of salivary glands. This leads to hypoplasia of the glands, a phenotype that is not rescued postnatally or by adulthood in both male and female Fgf10 +/- mice. Histological analysis of the glands showed no obvious defect in cellular differentiation or acini/ductal arrangements, however there was a significant reduction in their size and weight. Analysis of saliva secretion showed that hypoplasia of the glands led to a significant reduction in saliva production in Fgf10 +/- adults, giving rise to a reduced saliva pellicle in the oral cavity of these mice. Mature mice were shown to drink more and in many cases had severe tooth wear. The Fgf10 +/- mouse is therefore a useful model to explore the causes and effects of xerostomia.
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