Control of region-specific intestinal metabolism and maintenance by PRDM16
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA495347 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10166256.fastq.gz | Fastqsanger.gz | |||
| SRR10166257.fastq.gz | Fastqsanger.gz | |||
| SRR10166258.fastq.gz | Fastqsanger.gz | |||
| SRR10166259.fastq.gz | Fastqsanger.gz | |||
| SRR10166260.fastq.gz | Fastqsanger.gz |
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Project description:This SuperSeries is composed of the SubSeries listed below.
2020-02-26 | GSE121014 | GEO
Project description:Mutation of the PRDM16 gene causes human dilated and noncompaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with postnatal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored. This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN.
2023-07-21 | PXD043601 | Pride
Project description:Embryonic neocortical cells were isolated from E14.5 WT mice, followed by TrypLE Express treatment and trituration to generate a single-cell suspension. Plasmid DNA was introduced into primary neocortical cells using Neon Transfection System. Next, neocortical neurospheres were cultured in serum-free media containing, then control and Prdm16-overexpressing cells were corrected after GFP sorting of 1 day cultures. We found that marked upregulation of modulators of mitochondrial metabolism and ROS balance in Prdm16 GOF cells
2017-04-03 | E-MTAB-5646 | biostudies-arrayexpress
Project description:The adult intestinal epithelium is maintained by a continuous replacement of differentiated cells from stem cells. Previous studies suggest that cellular metabolic pathways regulate intestinal stem cell activity and differentiation. However, little is known about the cell-intrinsic factors that control these metabolic programs. Here, we identify the transcription factor PRDM16 as a critical regulator of intestinal metabolic programing and stem cell differentiation. Acute deletion of Prdm16 in adult mice causes severe intestinal wasting, apoptosis, and an accumulation of poorly differentiated cells in the crypt. Prdm16-deficient crypts display decreased expression levels of fatty acid oxidation (FAO) genes and reduced rates of FAO. PRDM16 binds, along with its protein partners PPARγ and PPARα, to the promoter and enhancer regions of many FAO genes. The loss of Prdm16 or inhibition of FAO impaired the transition of intestinal stem cells into transit amplifying cells. Notably, PRDM16 expression is highest in the duodenum and declines distally along the intestine. This gradient of PRDM16 expression controls the region-specific expression of the FAO program and underlies the differential reliance of region-specific stem cells on FAO. Altogether, this study establishes PRDM16 as a regional-specific regulator of metabolism and stem cell differentiation in the intestine.
2020-02-26 | GSE121009 | GEO
Project description:The adult intestinal epithelium is maintained by a continuous replacement of differentiated cells from stem cells. Previous studies suggest that cellular metabolic pathways regulate intestinal stem cell activity and differentiation. However, little is known about the cell-intrinsic factors that control these metabolic programs. Here, we identify the transcription factor PRDM16 as a critical regulator of intestinal metabolic programing and stem cell differentiation. Acute deletion of Prdm16 in adult mice causes severe intestinal wasting, apoptosis, and an accumulation of poorly differentiated cells in the crypt. Prdm16-deficient crypts display decreased expression levels of fatty acid oxidation (FAO) genes and reduced rates of FAO. PRDM16 binds, along with its protein partners PPAR? and PPAR?, to the promoter and enhancer regions of many FAO genes. The loss of Prdm16 or inhibition of FAO impaired the transition of intestinal stem cells into transit amplifying cells. Notably, PRDM16 expression is highest in the duodenum and declines distally along the intestine. This gradient of PRDM16 expression controls the region-specific expression of the FAO program and underlies the differential reliance of region-specific stem cells on FAO. Altogether, this study establishes PRDM16 as a regional-specific regulator of metabolism and stem cell differentiation in the intestine.
2020-02-26 | GSE120897 | GEO
Project description:Metabolic pathways dynamically regulate tissue development and maintenance. However, the mechanisms that govern the metabolic adaptation of stem or progenitor cells to their local niche are poorly understood. Here, we define the transcription factor PRDM16 as a region-specific regulator of intestinal metabolism and epithelial renewal. PRDM16 is selectively expressed in the upper intestine, with enrichment in crypt-resident progenitor cells. Acute Prdm16 deletion in mice triggered progenitor apoptosis, leading to diminished epithelial differentiation and severe intestinal atrophy. Genomic and metabolic analyses showed that PRDM16 transcriptionally controls fatty acid oxidation (FAO) in crypts. Expression of this PRDM16-driven FAO program was highest in the upper small intestine and declined distally. Accordingly, deletion of Prdm16 or inhibition of FAO selectively impaired the development and maintenance of upper intestinal enteroids, and these effects were rescued by acetate treatment. Collectively, these data reveal that regionally specified metabolic programs regulate intestinal maintenance.
| S-EPMC6898778 | biostudies-literature
Project description:Regulation of quiescence is critical for the maintenance of adult hematopoietic stem cells (HSCs). Previous studies by gene disruption during mouse embryonic development have shown that transcription factor gene Prdm16 is important for the generation/maintenance of fetal liver HSCs; however, the underlying mechanisms and the function of Prdm16 in adult HSCs remain unclear. To investigate the role of Prdm16 in adult HSCs, we generated a novel conditional knockout mouse model and deleted Prdm16 in adult mouse hematopoietic system using the interferon inducible Mx1-Cre. Our results show that deletion of Prdm16 leads to a gradual decline of adult HSC numbers and a concomitant increase in the multipotent progenitor (MPP) compartment. Prdm16 deletion in the hematopoietic system following transplantation produced the same phenotype indicating that the defect is intrinsic to the HSCs. This HSC loss was also exacerbated by stress induced by 5-FU injections. Annexin V staining showed no difference in apoptosis between wild type and knockout HSCs. In contrast, BrdU analysis revealed that loss of Prdm16 significantly increases cycling of long-term HSCs (LT-HSCs) with majority of the cells found in the S to G2/M phase. Consistently, RNA-seq analysis of mouse LT- HSCs with and without Prdm16 deletion showed that Prdm16 loss induced a significant decrease in the expression of several known cell cycle regulators of HSCs, among which Cdkn1a and Egr1 were further identified as direct targets of Prdm16. Our results suggest that Prdm16 preserves the function of adult LT-HSCs by promoting their quiescence.
2021-11-22 | GSE154011 | GEO
Project description:Background: Mutation of the PRDM16 gene causes human dilated and noncompaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with postnatal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored. Methods: This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN. Results: Prdm16csp1/wt mice are viable up to 8 months, develop hypoplastic hearts, and diminished systolic performance that is more pronounced in female mice. Prdm16csp1/wt cardiac tissue of both sexes showed reductions in metabolites associated with amino acid as well as glycerol metabolism, glycolysis, and the tricarboxylic acid cycle. Prdm16csp1/wt cardiac tissue revealed diminished glutathione (GSH) and increased inosine monophosphate (IMP) levels indicating oxidative stress and a dysregulated energetics, respectively. An accumulation of triacylglycerides exclusively in male Prdm16csp1/wt hearts, suggests a sex-specific metabolic adaptation. Metabolic modelling using CARDIOKIN identified a reduction in fatty acid utilization in males as well as lower glucose utilization in female Prdm16csp1/wt cardiac tissue. On the level of transcripts and protein expression, Prdm16csp1/wt hearts demonstrate an upregulation of pyridine nucleotide-disulphide oxidoreductase domain 2 (Pyroxd2) and the transcriptional regulator pre B-cell leukemia transcription factor interacting protein 1 (Pbxip1). The strongest concordant transcriptional upregulation was detected for Prdm16 itself, probably through an autoregulatory mechanism. Conclusions: Monoallelic, global Prdm16 mutation diminishes cardiac performance in Prdm16csp1/wt mice. Metabolic alterations and transcriptional dysregulation in Prdm16csp1/wt affect cardiac tissue. Female Prdm16csp1/wt mice develop a more pronounced phenotype, indicating sexual dimorphism at this early pathological window. This study suggests that metabolic dysregulation is an early event in the PRDM16 associated cardiac pathology.
2023-07-12 | GSE236791 | GEO
Project description:Gene expression profile from brown adipose tissues of Prdm16 knockout and wile type mice. Prdm16 is a transcription factor that regulates the thermogenic gene program in brown and beige adipocytes. However, whether Prdm16 is required for the development or physiological function of brown adipose tissue (BAT) in vivo has been unclear. By analyzing mice that selectively lacked Prdm16 in the brown adipose lineage, we found that Prdm16 was dispensable for embryonic BAT development. Brown adipose tissues were collected from Prdm16 knockout and wiletype mice with 4 biological replicates per condition. Experiment was done in two separate batch for 6-week-old and 11-month-old. Extracted RNA was hybridized to Agilent two-color arrays.
2014-04-09 | E-GEOD-55080 | biostudies-arrayexpress
Project description:Recent large-scale data sets indicate the emerging importance of alterations of the epigenome in renal cell carcinoma (RCC). Analysis of transcriptomic data of patient samples including normal kidney, primary tumor, and metastatic tumor deposits demonstrates epigenetic silencing of the gene encoding the transcription factor PR domain-containing 16 (PRDM16). PRDM16 has a prominent role in adipocyte metabolism but is also highly expressed in the kidney. The role of PRDM16 in renal cancer has not been investigated. RNAseq analysis reveals that PRDM16 imparts a predominantly repressive effect on the RCC transcriptome including suppression of SEMA5B (semaphorin 5B), a target gene of hypoxia inducible factor (HIF). Collectively, our data uncover a novel epigenetic basis by which HIF target gene expression is amplified in kidney cancer. Moreover, they demonstrate a new mechanism by which PRDM16 exerts its tumor suppressive effects.
2020-03-20 | GSE130049 | GEO