Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cited4a limits CM dedifferentiation and proliferation during zebrafish heart regeneration [Bulk RNA-seq]

ABSTRACT: Cardiac regeneration involves interplay of complex interactions between many different cell types, including cardiomyocytes. The exact mechanism that enables cardiomyocytes to undergo dedifferentiation and proliferation to replace lost cells has been under intense study. Here we report single nuclear RNA sequencing profile of the injured zebrafish heart and identified distinct cardiomyocyte populations in the injured heart. These cardiomyocyte populations indicate diverse functions that includes stress-response, myofibril assembly, proliferation and contraction. The contracting cardiomyocyte population also involves activation of maturation pathways as an early response to injury. This intriguing finding suggests that constant maintenance of distinctive terminally differentiated cardiomyocyte population is important for cardiac function during regeneration. To test this, we determined that cited4a, a p300/CBP transcriptional co-activator, is induced after injury in mature cardiomyocyte population. Moreover, loss-of-cited4a mutants showed increased dedifferentiation, proliferation and accelerated heart regeneration. Thus, suppressing cardiomyocyte maturation pathway activity in injured hearts could be an approach to promote heart regeneration.

ORGANISM(S): Danio rerio

PROVIDER: GSE279843 | GEO | 2025/01/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

cited4a limits CM dedifferentiation and proliferation during zebrafish heart regeneration [snRNA-seq]

Project description:Cardiac regeneration involves interplay of complex interactions between many different cell types, including cardiomyocytes. The exact mechanism that enables cardiomyocytes to undergo dedifferentiation and proliferation to replace lost cells has been under intense study. Here we report single nuclear RNA sequencing profile of the injured zebrafish heart and identified distinct cardiomyocyte populations in the injured heart. These cardiomyocyte populations indicate diverse functions that includes stress-response, myofibril assembly, proliferation and contraction. The contracting cardiomyocyte population also involves activation of maturation pathways as an early response to injury. This intriguing finding suggests that constant maintenance of distinctive terminally differentiated cardiomyocyte population is important for cardiac function during regeneration. To test this, we determined that cited4a, a p300/CBP transcriptional co-activator, is induced after injury in mature cardiomyocyte population. Moreover, loss-of-cited4a mutants showed increased dedifferentiation, proliferation and accelerated heart regeneration. Thus, suppressing cardiomyocyte maturation pathway activity in injured hearts could be an approach to promote heart regeneration.

2025-01-31 | GSE279845 | GEO

Murine neonatal cardiac B cells promote cardiomyocyte proliferation and heart regeneration

Project description:Since the proliferative capacity of cardiomyocytes is extremely limited in the adult mammalian hearts, the irreversible loss of cardiomyocytes following cardiac injury markedly reduces cardiac function, leading to cardiac remodeling and heart failure. However, the early neonatal mice have a strong ability in cardiomyocyte proliferation and cardiac regeneration after heart damage such as apical resection. Besides of cardiomyocytes, non-myocytes in heart tissue also play important roles in the regeneration process. Previous studies showed that cardiac macrophages, regulatory T cells and CD4+ T cells are all involved in regulating the myocardial regeneration process. However, the roles of other cardiac immune cells in cardiac regeneration remains to be elucidated. B cells is a prominent immune cell in injured heart; here we discovered the indispensable function of cardiac B cells in improving cardiomyocyte proliferation and heart regeneration in neonatal mice.

2023-06-02 | GSE205115 | GEO

Stimulation of glycolysis promotes cardiomyocyte proliferation after injury in adult zebrafish

Project description:Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac function. However, the role of metabolism in different aspects of cardiomyocyte regeneration remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNAs encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), especially in tissues bordering the damaged area. We further find that impaired glycolysis decreases the number of proliferating cardiomyocytes following injury. These observations are supported by analyses using loss-of-function models for the metabolic regulators Pkma2 and peroxisome proliferator-activated receptor gamma coactivator 1 alpha. Cardiomyocyte-specific loss- and gain-of-function manipulations of pyruvate metabolism using Pdk3 as well as a catalytic subunit of the pyruvate dehydrogenase complex (PDC) reveal its importance in cardiomyocyte dedifferentiation and proliferation after injury. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK-PDC axis in cardiomyocyte behavior following cardiac injury.

2020-07-13 | PXD016235 | Pride

Single-cell analysis of non-myocytes during heart regeneration reveals sequential coordinated responses from distinct cell populations [bulk RNA-seq]

Project description:Cardiac regeneration occurs primarily through proliferation of existing cardiomyocytes, yet the regenerative response also involves complex interactions between distinct cardiac cell types including not only cardiomyocytes, but also non-cardiomyocytes (nonCMs). However, the molecular features and cellular functions of the highly heterogeneous populations of nonCMs and how these populations cooperate to regenerate the injured heart remain largely unexplored. Using the newly developed LIGER algorithm that allows flexible modeling across highly diverse single-cell datasets, we analyzed the transcriptome dynamics of 61,977 individual nonCMs isolated at multiple time points during zebrafish heart regeneration. Combining single-cell analysis and in situ hybridization, we identified major nonCM cell types, including multiple novel subpopulations with unique tempo-spatial distributions and highly cooperative interactions in the regenerating heart. Interestingly, genetic perturbation of macrophage function by kit knockout led to accumulation of fibrotic deposits and severely compromised cardiomyocyte proliferation and myocardium regeneration. Our single-cell transcriptomic analysis of nonCMs during cardiac regeneration provides a blueprint for interrogating the molecular and cellular basis of cardiac regeneration.

2021-09-06 | GSE145979 | GEO

Single-cell analysis of non-myocytes during heart regeneration reveals sequential coordinated responses from distinct cell populations [scRNA-seq]

2021-09-06 | GSE145980 | GEO

Genomeâ??wide transcriptional profiling with spatial resolution identifies Bone Morphogenetic Protein signaling as essential regulator of zebrafish cardiomyocyte regeneration.

Project description:In contrast to mammals, zebrafish regenerate heart injuries via proliferation of cardiomyocytes located at the wound border. Here, we show that tomo-seq can be used to identify whole-genome transcriptional profiles of the injury zone, the border zone and the healthy myocardium. Interestingly, the border zone is characterized by the re-expression of embryonic cardiac genes that are also activated after myocardial infarction in mouse and human, including targets of Bone Morphogenetic Protein (BMP) signaling. Endogenous BMP signaling has been reported to be detrimental to mammalian cardiac repair. In contrast, we find that genetic or chemical inhibition of BMP signaling in zebrafish reduces cardiomyocyte dedifferentiation and proliferation, ultimately compromising myocardial regeneration, while bmp2b overexpression is sufficient to enhance it. Our results provide a resource for further studies on the molecular regulation of cardiac regeneration and reveal intriguing differential cellular responses of cardiomyocytes to a conserved signaling pathway in regenerative versus non-regenerative hearts. To generate spatially-resolved RNA-seq data for injured zebrafish hearts (3 and 7 days-post-injury), we cryosectioned samples, extracted RNA from the individual sections, and amplified and barcoded mRNA using the CEL-seq protocol (Hashimshony et al., Cell Reports, 2012) with a few modifications. Libraries were sequenced on Illumina NextSeq using 75bp paired end sequencing.

2016-01-11 | E-GEOD-74652 | biostudies-arrayexpress

Interspecies comparison reveals Hmga1 as driver of cardiac regeneration [scRNA-seq]

Project description:The prospect of repairing the heart after a myocardial infarction by promoting cardiomyocyte proliferation has gained momentum from studies showing the heart's regenerative ability in fish, amphibians and neonatal mammals. Despite evidence of varying cardiomyocyte proliferation rates among species, the molecular mechanisms driving cardiomyocyte cell cycle re-entry remain insufficiently understood. In this study, we employed spatial transcriptomics and identified high-mobility group AT-hook 1a (Hmga1a) as being upregulated in cardiomyocytes of the injury border zone in zebrafish, but not in mice. Through knock-out and cardiomyocyte-specific overexpression of hmga1a, we found that Hmga1a was required for zebrafish heart regeneration and sufficient to drive cardiomyocyte proliferation. In addition, a single injection of Hmga1 virus in injured mouse hearts resulted in increased border zone cardiomyocyte proliferation and improved heart function. Mechanistically, Hmga1 expression reduced repressive H3K27me3 histone modifications from developmentally-regulated genes and induced a border zone-like transcriptional program in adult cardiomyocytes. Our study demonstrates the value of interspecies comparisons by identifying Hmga1 as a critical driver of heart regeneration and highlights Hmga1 as a promising therapeutic candidate to improve cardiac repair after injury.

2024-11-15 | GSE241390 | GEO