Transcriptional profiles of kidney upon HNF4A loss in mice by RNA-seq
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE157911 | GEO | 2021/03/15
REPOSITORIES: GEO
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Project description:Knockout of HNF4A in yolk sac resulted in decreased expression levels of brush border genes and increased expression levels of stress fiber genes.
2021-03-15 | GSE166125 | GEO
Project description:The transcriptional regulation of drug-metabolizing enzymes and transporters (here collectively referred to as DMEs) in the developing proximal tubule is not well understood. As in the liver, DME regulation in the PT may be mediated through nuclear receptors which are thought to “sense” deviations from homeostasis by being activated by ligands, some of which are handled by DMEs, including drug transporters. Systems analysis of transcriptomic data during kidney development predicted a set of upstream transcription factors, including Hnf4a and Hnf1a, as well as Nr3c1 (Gr), Nfe2l2 (Nrf2), Ppara, and Tp53. Motif analysis of cis-regulatory further suggested that Hnf4a and Hnf1a are the main transcriptional regulators in the PT. Available expression data from tissue-specific Hnf4a KO tissues revealed that distinct subsets of DMEs were regulated by Hnf4a in a tissue-specific manner. ChIP-seq was performed to characterize the PT-specific binding sites of Hnf4a in rat kidneys at three developmental stages (prenatal, immature, adult), which further supported a major role for Hnf4a in regulating PT gene expression, including DMEs. In ex vivo kidney organ culture, an antagonist of Hnf4a (but not a similar inactive compound) led to predicted changes in DME expression, including among others Fmo1, Cyp2d2, Cyp2d4, Nqo2, as well as organic cation transporters and organic anion transporters Slc22a1(Oct1), Slc22a2 (Oct2), Slc22a6 (Oat1), Slc22a8(Oat3), and Slc47a1(Mate1). Conversely, overexpression of Hnf1a and Hnf4a in primary mouse embryonic fibroblasts (MEFs), sometimes considered a surrogate for mesenchymal stem cells, induced expression of several of these proximal tubule DMEs, as well as epithelial markers and a PT-specific brush border marker Ggt1. These cells had organic anion transporter function. Taken together, the data strongly supports a critical role for HNF4a and Hnf1a in the tissue-specific regulation of drug handling and differentiation toward a PT cellular identity. Hnf4a binding was examined in rat kidneys at three timepoints (E20, P13 and Adult) and p300 binding was examined in adult rat kidney cortex tissue using ChIP-seq. Four corresponding input DNA samples were used as controls for peak calling.
2014-01-01 | E-GEOD-50815 | biostudies-arrayexpress
Project description:The transcriptional regulation of drug-metabolizing enzymes and transporters (here collectively referred to as DMEs) in the developing proximal tubule is not well understood. As in the liver, DME regulation in the PT may be mediated through nuclear receptors which are thought to “sense” deviations from homeostasis by being activated by ligands, some of which are handled by DMEs, including drug transporters. Systems analysis of transcriptomic data during kidney development predicted a set of upstream transcription factors, including Hnf4a and Hnf1a, as well as Nr3c1 (Gr), Nfe2l2 (Nrf2), Ppara, and Tp53. Motif analysis of cis-regulatory further suggested that Hnf4a and Hnf1a are the main transcriptional regulators in the PT. Available expression data from tissue-specific Hnf4a KO tissues revealed that distinct subsets of DMEs were regulated by Hnf4a in a tissue-specific manner. ChIP-seq was performed to characterize the PT-specific binding sites of Hnf4a in rat kidneys at three developmental stages (prenatal, immature, adult), which further supported a major role for Hnf4a in regulating PT gene expression, including DMEs. In ex vivo kidney organ culture, an antagonist of Hnf4a (but not a similar inactive compound) led to predicted changes in DME expression, including among others Fmo1, Cyp2d2, Cyp2d4, Nqo2, as well as organic cation transporters and organic anion transporters Slc22a1(Oct1), Slc22a2 (Oct2), Slc22a6 (Oat1), Slc22a8(Oat3), and Slc47a1(Mate1). Conversely, overexpression of Hnf1a and Hnf4a in primary mouse embryonic fibroblasts (MEFs), sometimes considered a surrogate for mesenchymal stem cells, induced expression of several of these proximal tubule DMEs, as well as epithelial markers and a PT-specific brush border marker Ggt1. These cells had organic anion transporter function. Taken together, the data strongly supports a critical role for HNF4a and Hnf1a in the tissue-specific regulation of drug handling and differentiation toward a PT cellular identity.
2014-01-01 | GSE50815 | GEO
Project description:Hnf4a is specifically expressed in developing proximal tubule cells in the newborn mouse kidney. In order to identify direct target genes of Hnf4a in the developing proximal tubules, we performed ChIP-Seq of Hnf4a in the mouse kidneys at P0.
2020-11-12 | GSE144824 | GEO
Project description:Autoimmune diseases that affect the kidney proximal tubule (PT) cause proteinuria and are implicated in the pathogenesis of kidney failure. Previous evidence demonstrated that circulating anti-brush border antibodies (ABBA) target megalin (LRP2) but whether other components of the PT drive autoimmunity was unknown. Here we investigate a patient with LRP2-negative ABBA disease, and applied immunoprecipitation, mass spectrometry, and confocal imaging to identify cubilin as a novel antigen associated with the autoimmune disorder.
2023-04-06 | PXD030159 | Pride
Project description:We performed bulk RNA-seq and compared complehensive gene expression profiles of kidney organoids induced from wild type, HNF4A-KO, HNF4G-KO, and HNF4A/4G-DKO iPS cell lines.
2023-10-23 | GSE226439 | GEO
Project description:Background & Aims: Hepatocyte nuclear factor 4A (HNF4A) is a master transcription factor (TF) in hepatocytes that regulates metabolism and differentiation. The mechanism of HNF4A in cancer progression remains unclear due to conflicting results observed in numerous studies. We aimed to address the roles of HNF4A in hepatocellular carcinoma (HCC). Methods: We established the HNF4A overexpression and knocking-down stable cells in HCCLM3 and Huh7, and compared the effects of HNF4A on HCC cells in different glucose supply conditions in vitro and in vivo. Pathway inhibitors treatment and phosphatase activity comparisons were performed for signaling pathway analysis. Gene levels in HCC tissues and the clinical information were collected from TCGA for survival analysis. Multiomics approaches including proteomics, TFRE and ChIP-seq were applied to identify HNF4A target genes. Rescue experiments were performed to verify the functions of the potential target genes. Results: We found HNF4A exhibited tumor-suppressive effects on proliferation and migration of HCC cells in glucose-sufficient conditions but tumor-promotive effects in glucose-insufficient conditions. This diverse functionality of HNF4A was dependent upon the AMPK pathway activity. Similarly, the prognosis predicted by HNF4A was also correlated with AMPKa expression level in HCC patients. The potential HNF4A target genes, including NEDD4 and RPS6KA2, are involved in the diverse functionality of HNF4A in response to AMPK activity status. Conclusions: The glucose supply status could be the potential decisive factor to determine functions of HNF4A on HCC cells. The switch of HNF4A between oncogene and tumor suppressor was determined by AMPK activation status, which was correlated with glucose levels.
2019-08-01 | GSE101553 | GEO
Project description:The goal of our study is to determine if Hnf4a is required for the formation of proximal tubules during kidney development.
2020-11-12 | GSE144772 | GEO
Project description:The goal of our study is to determine if Hnf4a is required for the formation of proximal tubules during kidney development.
2018-09-24 | GSE112828 | GEO