Leptin b and its regeneration enhancer illustrate regenerative features of zebrafish hearts
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ABSTRACT:
PROVIDER: PRJNA821202 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18518538.fastq.gz | Fastqsanger.gz | |||
| SRR18518539.fastq.gz | Fastqsanger.gz | |||
| SRR18518540.fastq.gz | Fastqsanger.gz | |||
| SRR18518541.fastq.gz | Fastqsanger.gz |
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Project description:We obtained uninjured and injured hearts transcritome profiles of wild-type and LEN deletion mutant zebrafish. Note that LEN is the leptin b-linked regenreation enhancer located about 6kb upstream of leptin b gene.
2022-04-03 | GSE199697 | GEO
Project description:BackgroundZebrafish possess a remarkable regenerative capacity, which is mediated by the induction of various genes upon injury. Injury-dependent transcription is governed by the tissue regeneration enhancer elements (TREEs). Here, we utilized leptin b (lepb), an injury-specific factor, and its TREE to dissect heterogeneity of noncardiomyocytes (CMs) in regenerating hearts.ResultsOur single-cell RNA sequencing (scRNA-seq) analysis demonstrated that the endothelium/endocardium(EC) is activated to induce distinct subpopulations upon injury. We demonstrated that lepb can be utilized as a regeneration-specific marker to subset injury-activated ECs. lepb+ ECs robustly induce pro-regenerative factors, implicating lepb+ ECs as a signaling center to interact with other cardiac cells. Our scRNA-seq analysis identified that lepb is also produced by subpopulation of epicardium (Epi) and epicardium-derived cells (EPDCs). To determine whether lepb labels injury-emerging non-CM cells, we tested the activity of lepb-linked regeneration enhancer (LEN) with chromatin accessibility profiles and transgenic lines. While nondetectable in uninjured hearts, LEN directs EC and Epi/EPDC expression upon injury. The endogenous LEN activity was assessed using LEN deletion lines, demonstrating that LEN deletion abolished injury-dependent expression of lepb, but not other nearby genes.ConclusionsOur integrative analyses identify regeneration-emerging cell-types and factors, leading to the discovery of regenerative features of hearts.
| S-EPMC10256838 | biostudies-literature
Project description:High-quality genome and methylomes illustrate features underlying evolutionary success of oaks.
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Project description:To determine whether lymphangiogenesis is required for cardiac regeneration, vegfc(hy-/-);vegfd(-/-) double mutants and control hearts were collected and analyzed at 180 days after cryoinjury, this corresponds to a time point when the regenerative response is normally completed in wild-type zebrafish. Surprisingly, the vast majority (~70%) of vegfc(hy-/-);vegfd(-/-) mutants, which completely lack cardiac lymphatics, were able to mount a complete regenerative response without any signs of fibrosis. We found that the cardiac regenerative response was impaired only in a subset (3/8) of vegfc(hy-/-);vegfd(-/-) mutants, which were characterized by large deposits of fibrotic scar tissue present at the injury site. To profile vegfc/d-dependent genetic pathways contributing to lymphangiogenesis in cardiac regeneration, we performed RNA-seq on cryosections from control and mutant ventricles at 180 days following cryoinjury. Overall, vegfc(hy-/-);vegfd(-/-) mutant ventricles were characterized by an up-regulation of pathways related to metabolism, inflammation, hemostasis, negative regulation of FGFR signaling, translation, protein maturation and nonsense mediated decay compared to control hearts. These findings are consistent with the cardiac hypertrophy phenotype in vegfc(hy-/-);vegfd(-/-) mutants. To determine the molecular basis of the regenerative capacity within the mutant fish population, we next compared the transcriptional profiles of vegfc(hy-/-);vegfd(-/-) mutant hearts that did not regenerate (n=3) with the profiles of mutant hearts which recovered completely (n=5) at 180 days post cryoinjury. The subset of vegfc(hy-/-);vegfd(-/-) mutant hearts that failed to regenerate were characterized by an enrichment of inflammatory pathways, in particular TRAF6-mediated IRF7 activation, interferon alpha beta signaling and regulation of IFNA signaling. These findings suggest that loss of the vegfc/d signaling axis causes a sustained and pronounced inflammatory response following injury. This change in the cardiac micro-environment seems to favor adverse conditions which impair the regenerative process.
2019-09-03 | GSE133129 | GEO
Project description:Axonal growth is limited or absent following peripheral or central nervous system injury respectively, inhibiting repair. The identification of novel growth-promoting molecular mechanisms is therefore a priority. In the search for dietary-dependent mechanisms that control neuronal regenerative ability, we found, via RNA sequencing, that growth-promoting intermittent fasting (IF) induced leptin expression in sensory neurons of the dorsal root ganglia (DRG). Surprisingly, leptin signalling, whose canonical function is to control energy homeostasis, was critical for the IF-dependent regenerative phenotype. In fact, neuronal conditional deletion of the leptin receptor significantly impaired the regenerative response elicited by IF. Overexpression of leptin in vivo in DRG neurons enhanced axonal regeneration following peripheral sciatic nerve crush (SNC) and central spinal cord injury. Lastly, RNA sequencing following leptin overexpression in DRG neurons showed a significant increase in regenerative gene expression and transcription after SCI, indicating a role for leptin in inducing a euchromatic, transcriptionally active environment that facilitates nervous system repair after injury.
2025-08-13 | GSE224284 | GEO
Project description:Axonal growth is limited or absent following peripheral or central nervous system injury respectively, inhibiting repair. The identification of novel growth-promoting molecular mechanisms is therefore a priority. In the search for dietary-dependent mechanisms that control neuronal regenerative ability, we found, via RNA sequencing, that growth-promoting intermittent fasting (IF) induced leptin expression in sensory neurons of the dorsal root ganglia (DRG). Surprisingly, leptin signalling, whose canonical function is to control energy homeostasis, was critical for the IF-dependent regenerative phenotype. In fact, neuronal conditional deletion of the leptin receptor significantly impaired the regenerative response elicited by IF. Overexpression of leptin in vivo in DRG neurons enhanced axonal regeneration following peripheral sciatic nerve crush (SNC) and central spinal cord injury. Lastly, RNA sequencing following leptin overexpression in DRG neurons showed a significant increase in regenerative gene expression and transcription after SCI, indicating a role for leptin in inducing a euchromatic, transcriptionally active environment that facilitates nervous system repair after injury.
2025-08-13 | GSE224220 | GEO
Project description:Previous studies have suggested that the heart may be capable of limited repair and regeneration in response to a focal injury while other studies indicate that the mammalian heart has no regenerative capacity. To further explore this issue, we performed a series of superficial and transmural myocardial injuries in C57BL/6 and MRL/MpJ adult mice. At defined time intervals following the respective injury (Days 3, 14, 30 and 60) we examined cardiac function using echocardiography, morphology, FACS cell sorting for BrdU positive cells and molecular signature using microarray analysis. We observed complete restoration of myocardial function in the superficial MRL cryoinjured heart and significantly less scar formation as compared to the injured hearts of C57BL/6 mice. Following a severe transmural myocardial injury, the MRL mouse has increased survival and decreased ventricular remodeling compared to the C57BL/6 mouse but without evidence of significant regeneration. The cytoprotective program observed in the severely injured MRL heart is in part due to increased vasculogenesis and decreased apoptosis that limits the extension of the injury. We conclude that C57BL/6 and MRL injured hearts have evidence of limited myocardial regeneration, in response to superficial injury, but the improved function and survival observed in the MRL mouse heart following severe injury is not due to significant regenerative processes. Mouse hearts from C57BL/6 and MRL/MpJ strains were injured with LAD ligation and harvested at 3, 30 and 60 days after treatement.
2007-11-23 | E-GEOD-4710 | biostudies-arrayexpress
Project description:We employed translating ribosome affinity purification followed by RNA sequencing to isolate and analyze mRNA from the hypothalamic LepRb neurons of wild-type or leptin-deficient (Lepob/ob) mice treated with vehicle or exogenous leptin. Although the expression of most of the genes encoding the neuropeptides commonly considered to represent the main targets of leptin action were altered only following chronic leptin deprivation, our analysis revealed other transcripts that were coordinately regulated by leptin under multiple treatment conditions. Among these, acute leptin treatment increased expression of the transcription factor Atf3 in LepRb neurons.
2020-12-03 | GSE162603 | GEO