Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

runx1 controls zebrafish heart regeneration by promoting scar deposition as well as inhibiting myocardial proliferation and survival

ABSTRACT: Runx1 is a transcription factor that plays a key role in determining the proliferative and differential state of multiple cell types, during both development and adulthood. Here, we report how runx1 is specifically upregulated at the injury site during zebrafish heart regeneration, but unexpectedly, absence of runx1 results in enhanced regeneration. Using single cell sequencing, we found that the wild-type injury site consists of Runx1-positive endocardial cells and thrombocytes that express smooth muscle and collagen genes without differentiating into myofibroblasts. Both these populations are absent in runx1 mutants, resulting in a less collagenous and fibrinous scar. The reduction in fibrin in the mutant is further explained by reduced myofibroblast formation and by upregulation of components of the fibrin degradation pathway, including plasminogen receptor Annexin 2A as well as downregulation of plasminogen activator inhibitor serpine1 in myocardium and endocardium, resulting in increased levels of Plasminogen. In addition, this we also find enhanced myocardial proliferation as well as increased myocardial survival in the mutant. Our findings suggest that Runx1 controls the regenerative response of multiple cardiac cell-types and that targeting Runx1 is a novel therapeutic strategy to induce endogenous heart repair.

ORGANISM(S): Danio rerio

PROVIDER: GSE138181 | GEO | 2020/04/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of injured mouse hearts from C57Bl/6 and MRL sampled at 3 time points to investigate the regenerative capacity of the mammalian heart

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

Accumulation of acylcarnitines and mitochondrial dysfunction characterize the loss of neonatal myocardial regeneration capacity

Project description:Myocardial regeneration capacity declines during the first week after birth and is linked to the adaptation to oxidative metabolism. Utilizing this regenerative window, we characterized the metabolic changes in myocardial injury in 1-day-old regeneration-competent and 7-day-old regeneration-compromised mice. The mice were either sham-operated or received left anterior descending coronary artery ligation, to induce myocardial infarction (MI) and acute ischemic heart failure. Myocardial tissue samples were collected after 21 days for metabolomics, transcriptomics and proteomics analyses. Phenotypic characterizations were carried out using echocardiography, histology as well as mitochondrial structural and functional measurements. By integrating the findings from metabolome and transcriptome examinations, we identified mitochondrial dysfunction at the level of the carnitine shuttle contributing to myocardial regeneration incompetence. Regeneration failure was linked to accumulation of acylcarnitines and insufficient metabolic capacity for fatty acid beta-oxidation. We further identified specific transcription factors and post-transcriptional regulation contributing to both regeneration competence and failure. Rather than shifting from the preferred myocardial oxidative fuel source, our results put forward the facilitation of mitochondrial fatty acid transport and improving the beta- oxidation pathway to overcome the metabolic barriers for repair and regeneration in adult mammals after MI and heart failure.

2022-02-04 | MSV000088783 | MassIVE

Neutrophils facilitate the epicardial regenerative response after zebrafish heart injury

Project description:Despite extensive studies on endogenous heart regeneration within the past 20 years, the players involved in initiating early regeneration events are far from clear. Here, we assessed the function of neutrophils, the first-responder cells to tissue damage, during heart regeneration. We detected rapid neutrophil mobilization to the injury site after ventricular amputation, peaking at 1-day post-amputation (dpa) and resolving by 3 dpa. Further analyses indicated neutrophil mobilization coincides with peak epicardial cell proliferation and recruited neutrophils associated with activated, expanding epicardial cells at 1 dpa. Neutrophil depletion inhibited myocardial regeneration and significantly reduced epicardial cell expansion, proliferation, and activation. To explore the molecular mechanism of neutrophils on the epicardial regenerative response, we performed scRNA-seq analysis of 1 dpa neutrophils and identified enrichment of the FGF and ERK signaling pathways. Pharmacological inhibition of FGF signaling indicated its’ requirement for epicardial cell expansion, while neutrophil depletion blocked ERK signaling activation in epicardial cells. Altogether, our studies revealed that neutrophils quickly induce epicardial cells, which later accumulate at the injury site and contribute to heart regeneration.

2024-07-09 | GSE237761 | GEO

Telomerase is essential for zebrafish heart regeneration

Project description:Unlike human hearts, zebrafish hearts efficiently regenerate after injury. Regeneration is driven by the strong proliferation response of its cardiomyocytes to injury. In this study, we show that active telomerase is required for cardiomyocyte proliferation and full organ recovery, supporting the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction. Heart transcriptomes of WT and telomerase defective adult zebrafish animals were profiled by RNASeq, in control conditions and 3 days after heart cryoinjury.

2015-08-06 | E-GEOD-71755 | biostudies-arrayexpress

Expression data from C57BL/6 and MRL/MpJ heart left ventrical with LAD ligation

2006-04-24 | GSE4710 | GEO

Activation of Nkx2.5 Transcriptional Program is Required for Adult Myocardial Repair

Project description:We show that cardiac-specific RNA-sequencing studies reveal a disrupted embryonic Nkx2.5 transcriptional profile despite histologically normal, Nkx2.5 loss-of-function adult myocardium. Yet, adult nkx2.5-/- fish exhibit an impaired ability to recover following ventricular apex amputation as illustrated by retention of fibrin and collagen in the injured area. Complex network analyses illuminate that Nkx2.5 is required to mount a proliferative response for cardiomyocyte renewal and to provoke proteolytic pathways necessary for sarcomere disassembly. Moreover, direct Nkx2.5 targets embedded in these distinct gene regulatory modules coordinate appropriate, multi-faceted injury responses. Altogether, our findings support a previously unrecognized, Nkx2.5-dependent regenerative circuit that invokes myocardial proliferation and dedifferentiation to ensure effective regeneration in the teleost heart.

2022-04-05 | GSE164966 | GEO

GNPS - Accumulation of acylcarnitines and mitochondrial dysfunction characterize the loss of neonatal myocardial regeneration capacity

2022-02-04 | MSV000088783 | GNPS

Site-specific N-glycan Analysis of Neonatal Mouse Hearts

Project description:The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury but lose it after a week of life, which has been utilized as a valuable model to explore the cues for heart regeneration. More and more researches indicated that glycoprotein played an important role in cardiac regeneration. Elucidating the glycosylation processes associated with heart regeneration will be beneficial for the molecular mechanism studies of heart regeneration as well as discovery of potential therapeutic strategies for human cardiac diseases. In this work, an integrated glycoproteomic and proteomic analysis were performed to investigate the differences in glycoprotein abundances and site-specific glycosylation occupancy between neonatal day 1 (P1) and day 7 (P7) of mouse hearts. The intact glycoepeptides were enriched and identified in both P1 and P7 hearts. To screen for differentially regulated glycoproteins, we compared the expression levels of intact glycopeptides between P1 and P7 hearts using label free quantification. Eventually, the glycosylation occupancy of site-specific N-glycans were obtained by comparing the alterations of intact glycopeptides with their corresponding protein expression levels obtained from global proteomic analysis. These altered glycosylation patterns among proteins between P1 and P7 mouse hearts have a significant potential to aid our understanding of the regenerative capacity loss in neonatal mouse hearts during the first week, thus leading to novel therapeutic approaches to recover the capacity.

2020-05-26 | PXD017139 | Pride