Loss of FGF9 in mice leads to pancreatic hypoplasia and asplenia
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ABSTRACT:
PROVIDER: PRJNA866543 | ENA |
REPOSITORIES: ENA
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Project description:Pancreatic development requires spatially and temporally controlled expression of growth factors derived from mesenchyme. Here, we report that in mice the secreted factor Fgf9 is expressed principally by mesenchyme and then mesothelium during early development, then subsequently by both mesothelium and rare epithelial cells by E12.5 and onwards. Global knockout of the Fgf9 gene resulted in the reduction of pancreas and stomach size, as well as complete asplenia. The number of early Pdx1+ pancreatic progenitors was reduced at E10.5, as was proliferation of mesenchyme at E11.5. Although loss of Fgf9 did not interfere with differentiation of later epithelial lineages, single-cell RNA-Sequencing identified transcriptional programs perturbed upon loss of Fgf9 during pancreatic development, including loss of the transcription factor Barx1. Lastly, we identified conserved expression patterns of FGF9 and receptors in human fetal pancreas, suggesting that FGF9 expressed by pancreatic mesenchyme may similarly affect the development of the human pancreas.
| S-EPMC10121468 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-03-28 | GSE210646 | GEO
Project description:Temporally and spatially coordinated epithelial–mesenchymal interactions are central to the development of the primitive gut tube endoderm and are necessary to form functional organs of the gastrointestinal tract, including the pancreas. Here, we examined the functional role of the secreted factor Fgf9 in murine pancreatic development. Single-cell RNA-sequencing was performed on embryonic day (E) 14.5 mouse pancreas from both wildtype and Fgf9 knockout embryos. Our data reveal shifts in cellular populations upon loss of Fgf9. In addition, we have identified specific transcriptional programs and signaling pathways perturbed in the context of loss of Fgf9 during pancreatic development.
2023-03-28 | GSE210645 | GEO
Project description:Temporally and spatially coordinated epithelial–mesenchymal interactions are central to the development of the primitive gut tube endoderm and are necessary to form functional organs of the gastrointestinal tract, including the pancreas. Here, we examined the functional role of the secreted factor Fgf9 in murine pancreatic development. Bulk RNA-sequencing was performed on embryonic day (E) 13.5 and 14.5 mouse pancreas from both wildtype and Fgf9 knockout embryos. Our data have identified specific transcriptional programs and signaling pathways perturbed in the context of loss of Fgf9 during pancreatic development.
2023-03-28 | GSE210574 | GEO
Project description:We have previously shown that FGF9 is overexpressed in hypoxia through the IRES located in the 5’UTR. To identify the protein that binds to FGF9 IRES and controls FGF9 protein synthesis in hypoxia, FGF9 IRES RNA was in vitro synthesized and used to pulled-down interacting proteins. The RNA-protein complexes were first visualized by sliver staining, followed by cutting specific bands for protein identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS).
2019-11-13 | PXD012892 | Pride
Project description:In this study, we found that Fgf9 regulates the bone-fat balance by modulating the cell fate determination of BMSCs. Histology and micro-CT analysis demonstrate that Fgf9 S99N mutation (loss-of-function) significantly inhibited the formation of bone marrow adipose tissue (BMAT) in adult mice and alleviated the ovariectomized (OVX) induced bone loss and BMAT accumulation. In vitro cytodifferentiation assays unveiled that the Fgf9 S99N mutation hindered adipogenesis while promoting osteogenesis in BMSCs. Furthermore, recombinant FGF9 stimulation and Fgf9 overexpression in BMSCs demonstrated that Fgf9 significantly promoted adipocyte formation and inhibited osteogenesis in vitro and in vivo. Cytodifferentiation assays at various stages of BMSC differentiation indicated that FGF9 altered the osteogenic and adipogenic potential of BMSCs, particularly during the early stages of differentiation. Transcriptomic and gene expression analyses demonstrated that FGF9 significantly upregulated the expression of adipogenic genes while downregulating osteogenic gene expression at both mRNA and protein levels. KEEG analysis revealed and in vitro differentiation assays with specific inhibitors confirmed that FGF9 modulated bone-fat balance by inhibiting osteogenesis via the MAPK/ERK pathway and promoting adipogenesis by activating the PI3K/AKT and Hippo pathways.
2024-07-17 | GSE252394 | GEO
Project description:Loss of the Mia40a oxidoreductase leads to hepato-pancreatic insufficiency in the zebrafish
| PRJNA450632 | ENA
Project description:Objectives: Fibroblast growth factor 9 (FGF9) is expressed by somatic cells in the seminiferous tubules, yet little information exists about its role in regulating spermatogonial stem cells (SSCs). Materials and Methods: Fgf9 overexpression lentivirus was injected into mouse testes, and PLZF immunostaining was performed to investigate the effect of FGF9 on spermatogonia in vivo. Effect of FGF9 on SSCs was detected by transplanting cultured germ cells into tubules of testes. RNA-seq of bulk RNA and single-cell was performed to explore FGF9 working mechanisms. SB203580 was used to disrupt p38 MAPK pathway. p38 MAPK protein expression was detected by western blot and qPCR was performed to determine different gene expression. Small interfering RNA (siRNA) was used to knock down Etv5 gene expression in germ cells. Results: Overexpression of Fgf9 in vivo resulted in arrested spermatogenesis and accumulation of undifferentiated spermatogonia. Exposure of germ cell cultures to FGF9 resulted in larger numbers of SSCs over time. Inhibition of p38 MAPK phosphorylation negated the SSC growth advantage provided by FGF9. Etv5 and Bcl6b gene expression was enhanced by FGF9 treatment. Gene knockdown of Etv5 disrupted the growth effect of FGF9 in cultured SSCs along with downstream expression of Bcl6b. Conclusions: Taken together, this data indicates that FGF9 is an important regulator of SSC proliferation, operating through p38 MAPK phosphorylation and upregulating Etv5 and Bcl6b in turn.
2020-10-26 | GSE160062 | GEO
Project description:To determine the role of Fgf9 in gastric development, we collected E15.5 Fgf9 KO (Fgf9LacZ/LacZ) and Het (Fgf9LacZ/+) stomachs for RNA-seq analysis. 3 stomachs were pooled for each RNA-seq sample.
2024-11-15 | GSE281156 | GEO
Project description:Background Congenital anomalies of the kidney and urinary tract (CAKUT) refer to a diverse group of developmental malformations, which are the leading cause of chronic kidney disease and end-stage renal disease in children. The etiology and pathogenesis of CAKUT are complex. In recent years, the relationship between long noncoding RNAs and renal development and disease has attracted much attention. Our previous study established a long noncoding RNA 4933425B07Rik (Rik) overexpression mouse model by inserting the PB transposon and found that overexpression of Rik led to renal hypoplasia. This study aimed to explore the molecular mechanism of renal hypoplasia induced by Rik overexpression in vitro. Results In this study, by constructing Rik overexpression cell models and a Rik knockout cell model to accompany previously developed RikPB/PB;Hoxb7 mice and by applying RNA-seq, RT‒PCR and other experimental methods, it was found that when Rik was highly expressed, the expression of Wnt10b, Fzd8 and β-catenin decreased, while Rik was knock down, the expression of these genes increased. Conclusions The findings suggest that overexpression of Rik leads to renal hypoplasia by inactivating the Wnt/β-catenin signaling pathway. This research perspective may provide a basis for exploring new causes and mechanisms of CAKUT and provide new targets for the prevention and treatment of CAKUT.
2022-08-30 | GSE212130 | GEO