Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393257 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:FGF23 has been known to play an important role of calcium-phosphorus (Ca-P) metabolism. Recently, biological roles of FGF23 other than Ca-P metabolism were reported, such as commitment to myocardium enlargement and immunological roles in spleen. Thus, it was thought FGF23 might have roles other than Ca-P metabolism in renal tubule epithelial cells. So, we tried to identify new biological roles of FGF23 in those cells using DNA microarray analysis in mouse renal tubule epithelial cell line, mIMCD3, with FGF23 stimulation. As the results, expressions of 8 genes were upregulated and those of 18 genes were downregulated in mIMCD3 with FGF23 stimulation compared to those in mIMCD3 without FGF23 stimulation. Three out of 8 upregulated genes were protein coding genes and remaining 5 genes were non protein coding genes. Fifteen out of 18 downregulated genes were protein coding genes and remaining 3 genes were non protein coding genes.
2018-04-18 | GSE100847 | GEO
Project description:FGF23 via its coreceptor αKlotho (KL) provides critical control of phosphate metabolism, which is altered in rare and very common syndromes. However, the spatial-temporal mechanisms dictating renal FGF23 functions remain poorly understood, thus developing approaches to modify specific FGF23-dictated pathways has proven problematic. Herein, wild type mice were injected with rFGF23 for 1, 4 and 12h and renal FGF23 bioactivity was determined at single cell resolution. Computational analysis identified distinct epithelial, endothelial, stromal, and immune cell clusters, with differential expressional analysis uniquely tracking FGF23 bioactivity at each time point. FGF23 actions were sex independent but critically relied upon constitutive KL expression mapped within proximal tubule (S1-S3) and distal tubule (DCT/CNT) cell sub-populations. Temporal KL-dependent FGF23 responses drove unique and transient cellular identities, including genes in key MAPK- and vitamin D-metabolic pathways via early- (AP-1-related) and late-phase (EIF2 signaling) transcriptional regulons. Combining ATACseq/RNAseq data from a cell line stably expressing KL with the in vivo scRNAseq pinpointed genomic accessibility changes in MAPK-dependent genes, including the identification of FGF23-dependent EGR1 distal enhancers. Finally, we isolated unexpected crosstalk between FGF23-mediated MAPK signaling and pro-inflammatory TNF receptor activation via NF-κB, which blocked FGF23 bioactivity in vitro and in vivo. Collectively, our findings have uncovered novel pathways at the single cell level that likely influence FGF23-dependent disease mechanisms.
2025-03-26 | GSE254541 | GEO
Project description:FGF23 is a bone-derived hormone that mediates renal phosphate reabsorption and 1,25(OH)2 vitamin D metabolism via its required co-receptor alpha-Klotho (KL). The functional pathways guiding this hormone’s activity in kidney have not been studied extensively, and whether using other factors with overlapping signaling profiles to produce FGF23-like responses is unclear. To map FGF23-related genes, gene array and single-cell RNA sequencing were utilized on wild type mouse kidneys. After identifying Heparin-binding EGF-like growth factor (HBEGF) as an up-regulated gene in response to FGF23 delivery, KL-null and phosphate-deficient diet fed mouse models and in vitro experiments were utilized to further test HBEGF bioactivity in kidney. Gene array demonstrated that HBEGF was significantly up-regulated following FGF23 delivery to wild type (WT) mice. Next, mice injected with HBEGF had phenotypes consistent with partial FGF23-mimetic activity including robust induction of EGR1, and increased CYP24A1 mRNAs. Single cell RNA sequencing showed overlapping HBEGF and EGFR expression in the proximal tubule (PT), and KL expression in PT and distal tubule (DT) segments. In KL-null mice devoid of canonical FGF23 signaling, HBEGF injections significantly increased EGR1 and CYP24A, and correction of basally-elevated CYP27B1 was observed. In addition, mice placed on a phosphate deficient diet to suppress FGF23 had endogenously increased CYP27B1 mRNA, which was rescued in mice receiving HBEGF. In HEK293 renal epithelial cells, HBEGF and FGF23 increased CYP24A1 mRNA. Targeting pathways known to be downstream of FGF23 in kidney may help to control renal phosphate handling in diseases of altered FGF23 bioactivity.
2020-10-01 | GSE138992 | GEO
Project description:Wild type mice were injected with rFGF23 for 1, 4 and 12h and renal FGF23 bioactivity was determined at single cell resolution. UMAP plots identified distinct epithelial, endothelial, stromal, and immune cell clusters, with differential expressional analysis uniquely tracking FGF23 bioactivity at each time point.
2025-03-26 | GSE246385 | GEO
Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other
2004-01-02 | GSE887 | GEO
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is essential for the development of the kidney. Mutations of HNF-1β produce autosomal dominant tubulointerstitial kidney disease (ADTKD) characterized by tubular cysts, renal fibrosis, and progressive decline in kidney function. To understand the functions of HNF-1β, we generated HNF-1β-deficient mIMCD3 renal epithelial cells. Gene editing with CRISPR/Cas9 was used to delete exon 1 of HNF-1β by non-homologous end joining (NHEJ). We performed RNA-seq on three independent HNF-1β-deficient mIMCD3 cell lines and three paired control cell lines. Our RNA-seq of HNF-1β-deficient cells showed upregulation of 1,135 genes and repression of 759 genes compared to control cells. Pathway analysis revealed that fibrosis and epithelial-mesenchymal transition (EMT) pathways were highly activated in HNF-1β-deficient cells. We conclude that loss of HNF-1β in renal epithelial cells leads to the activation of a transcriptional network that induces EMT and aberrant TGFβ signaling. Targeting this network may inhibit fibrosis in ADTKD and other chronic kidney diseases.
2018-08-10 | GSE97770 | GEO
Project description: Not available
| S-EPMC11335981 | biostudies-literature
Project description: Not available
| S-EPMC4490682 | biostudies-literature
Project description: Not available
| S-EPMC395764 | biostudies-literature