Downregulation of Scd1 promotes cardiac reprogramming by enhancing mitochondrial metabolism through PGC1α [RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1201855 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31805806_1.fastq.gz | Fastqsanger.gz | |||
| SRR31805806_2.fastq.gz | Fastqsanger.gz | |||
| SRR31805807_1.fastq.gz | Fastqsanger.gz | |||
| SRR31805807_2.fastq.gz | Fastqsanger.gz | |||
| SRR31805808_1.fastq.gz | Fastqsanger.gz |
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Project description:Downregulation of Scd1 promotes cardiac reprogramming by enhancing mitochondrial metabolism through PGC1α
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Project description:Direct cardiac reprogramming of fibroblasts into induced cardiac-like myocytes (iCMs) has emerged as a promising therapeutic strategy to remuscularize injured myocardium. However, the intrinsic metabolic demands that drive the iCM program and maturity remain unclear. Here, we induce efficient iCM production and maturation through metabolic pathway modulations. We show that the knockdown of Stearoyl-CoA desaturase 1 (Scd1) facilitates cardiac reprogramming and functional maturation of iCM. Through Bulk-RNAseq analysis, we found that compared with control group, fibrosis and inflammatory response pathway were significantly down-regulated, while cardiac related features and fatty acid metabolism related genes were up-regulated in shscd1 group. We further observed the expression level of PGC1α which serves as a master regulator of mitochondrial biogenesis and function was significantly increased in shScd1 group from RNA-seq. Mechanistically, we proved that Scd1 knockdown activates PGC1α/PPARβ transcription signal, which further promotes cardiac reprogramming, and induced cardiomyocytes demonstrated more frequent beating, calcium oscillation, and higher energy metabolism as evidenced by increased mitochondrial respiration and gene expression associated with FAO, which provides a new strategy and theoretical basis for cardiac regeneration and repair
2025-04-23 | GSE271439 | GEO
Project description:Direct cardiac reprogramming of fibroblasts into induced cardiac-like myocytes (iCMs) has emerged as a promising therapeutic strategy to remuscularize injured myocardium. However, the intrinsic metabolic demands that drive the iCM program and maturity remain unclear. Here, we induce efficient iCM production and maturation through metabolic pathway modulations. To explore the metabolic heterogeneity of iCMs, we performed single cell RNA sequencing (scRNA-seq) at reprograming day 14. Using single-cell metabolic flux estimation and flux balance analysis on day 14 iCM, we characterized the metabolic heterogeneity of iCMs and identified fatty acid oxidation (FAO) as a critical factor in iCM conversion. Mechanistically, we proved that Scd1 knockdown activates PGC1α/PPARβ transcription signal, which further promotes cardiac reprogramming, and induced cardiomyocytes demonstrated more frequent beating, calcium oscillation, and higher energy metabolism as evidenced by increased mitochondrial respiration and gene expression associated with FAO, which provides a new strategy and theoretical basis for cardiac regeneration and repair. Our findings collectively highlight FAO as a key determinant of iCM fate and offer new therapeutic avenues for advancing reprogramming strategies.
2025-04-23 | GSE285211 | GEO
Project description:Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC1α) is a coactivator of various nuclear receptors and other transcription factors that shows increased expression in skeletal muscle during exercise. In skeletal muscle, PGC1α is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Several isoforms of PGC1α mRNA have recently been identified. PGC1α-a is a full-length isoform of PGC1α that was the first to be isolated. PGC1α-b is another isoform of PGC1α, which is considered to be similar in function to PGC1α-a, differing by only 16 amino acids at the amino terminus. We have previously generated independent lines of transgenic mice that overexpress PGC1α-a or PGC1α-b in skeletal muscle. The microarray data shows that energy metabolism-related pathways such as the TCA cycle, branched-chain amino acid metabolism, purine nucleotide pathway, and malate–aspartate shuttle are activated in PGC1α transgenic mice compared with wild-type mice. For microarray analysis, RNA was isolated from the gastrocnemius skeletal muscle of wild-type control mice (12 weeks of age) as well as transgenic mice [PGC1α-a (E) (Miura et al., J. Biol. Chem. 278:31385-90, 2003), 12 weeks of age; PGC1α-b (02-1) (Miura et al., Endocrinology 149:4527-33, 2008), 14 weeks of age; and PGC1α-b (03-2) (Miura et al., Endocrinology 2008), 14 weeks of age]. Samples from wild-type and transgenic mice (N = 5 for each group) were pooled before use.
2015-09-18 | E-GEOD-67049 | biostudies-arrayexpress
Project description:PGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia microscopy revealed that intimal injury disrupted the balance of vascular energy metabolism and impaired the mitochondrial ultrastructure in vivo. The human carotid plaque and femoral artery plaque samples also exhibited alterations in mitochondrial morphology. Vascular smooth muscle cells (VSMCs) are the main components of neointimal hyperplasia and are subjected to cyclic stretch resulting from pulsatile pressure. In this study, we found that the application of cyclic stretch in vitro increased VSMC mitochondrial mass and function. In addition, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α) played an important role in regulating VSMC mitochondrial function in response to physiological stretch via the phosphorylation of Smad3. Increasing the activation of PGC1α by ZLN005 treatment effectively inhibited VSMC hyperproliferation after intimal injury in vivo. These results suggested that the regulation of PGC1α by p-Smad3 in response to physiological cyclic stretch may effectively alleviate neointimal hyperplasia by promoting mitochondrial function. PGC1α may be a potential therapeutic target for the prevention and treatment of neointimal hyperplasia.
2025-08-13 | GSE285663 | GEO
Project description:Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC1α) is a coactivator of various nuclear receptors and other transcription factors that shows increased expression in skeletal muscle during exercise. In skeletal muscle, PGC1α is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Several isoforms of PGC1α mRNA have recently been identified. PGC1α-a is a full-length isoform of PGC1α that was the first to be isolated. PGC1α-b is another isoform of PGC1α, which is considered to be similar in function to PGC1α-a, differing by only 16 amino acids at the amino terminus. We have previously generated independent lines of transgenic mice that overexpress PGC1α-a or PGC1α-b in skeletal muscle. The microarray data shows that energy metabolism-related pathways such as the TCA cycle, branched-chain amino acid metabolism, purine nucleotide pathway, and malate–aspartate shuttle are activated in PGC1α transgenic mice compared with wild-type mice.
2015-09-18 | GSE67049 | GEO
Project description:To understand molecular mechanisms underlying the growth inhibitory ativity of Stearoyl-CoA desaturase-1 (SCD1) inhibitor, we performed microarray analysis using HCT-116 colorectal cancer cells, in which SCD1 was pharmacologically blocked or genetically ablated.
2017-08-01 | GSE98364 | GEO
Project description:Niche for stem cells can profoundly influence the position and fate of stem cells in tissue homeostasis and associated disorders, however, the mechanisms underlying the maintenance of stem cell niche remain poorly understood. Here we report that fatty acid desaturation catabolized by stearoyl-coenzyme A desaturase 1 (SCD1) regulates the activity of hair follicle stem cells (HFSCs) via blocking the formation of the bulge, a niche for HFSCs. We further unraveled that the abnormal hair growth in mice with SCD1 deletion is due to its function in K14+ basal keratinocytes rather than directly affecting HFSCs. Mechanistically, SCD1 deficiency impaired the expression of integrin α6 and the formation of hemidesmosomes (HDs), and thus allowed the activation of FAK in K14+ keratinocytes. Activated FAK subsequently stimulated PI3K and promoted the differentiation and proliferation of these keratinocytes, resulting in downward extension of the outer root sheath (ORS) and the disruption of bulge formation. Interestingly, inhibition of PI3K signaling restored bulge formation and normalized HFSCs and hair growth. Supplementation of oleic acid, the product of SCD1, to SCD1-/- mice also enhanced HD numbers, normalized the niche of HFSCs, and promoted hair growth in SCD1-/- mice. Taken together, SCD1 is indispensable for hair growth through stabilizing the number of HDs and thus sustaining bulge formation for HFSC residence and periodic activity.
2023-02-08 | GSE184346 | GEO
Project description:Stearoyl-CoA desaturase 1-deficient (SCD1-/-) mice have impaired monounsaturated fatty acid (MUFA) synthesis. When maintained on a very low-fat, high-carbohydrate (VLF-HC) diet, SCD1-/- mice develop severe hypercholesterolemia characterized by an increase in apolipoprotein B-containing lipoproteins and the appearance of lipoprotein-X. Additionally, high-density lipoprotein cholesterol is dramatically reduced in VLF-HC SCD1-/- mice. The concomitant presence of elevated plasma bile acids, bilirubin and aminotransferases in the VLF-HC SCD1-/- mouse are indicative of hepatic dysfunction. Supplementation of the VLF-HC diet with unsaturated fat (canola oil), but not saturated fat (coconut oil), prevents these plasma phenotypes. However, dietary oleate was not as effective as canola oil in reducing low-density lipoprotein cholesterol, signifying an additional role for dietary polyunsaturated fatty acid deficiency in the development of this phenotype. These results indicate that lack of SCD1 results in an increased requirement for dietary unsaturated fat to compensate for impaired MUFA synthesis and to prevent hypercholesterolemia and hepatic dysfunction. Keywords: repeat (genotype and diet)
2005-12-23 | GSE3889 | GEO
Project description:Escherichia coli SCD1 Genome sequencing and assembly
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