run_metadata: 25207
This data as json
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| 25207 | SRR25685551 | SRX21410745 | SRS18649227 | SRP455779 | PRJNA1006658 | Interspecies comparison reveals Hmga1 as driver of cardiac regeneration [bulk RNAseq Hmga1a OE] | GSE241157 | Transcriptome Analysis | The prospect of repairing the heart post 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 xxx post injury. Overall design: TOMOseq was performed on mouse and zebrafish hearts at 3 7 and 14 xxx post injury for the interspecies comparison. single cell RNA sequencing was performed on wildtype versus hmga1a mutant zebrafish cardiomyocytes 7 days post cryoinjury to assess differences during heart regeneration. Bulk RNA sequencing was performed on control versus Hmga1a overexpression cardiomyocytes to assess the effect in an uninjured heart. bulk sortChIC sequencing was performed on control versus Hmga1a overexpression cardiomyocytes to assess the effect of Hmga1a on the chromatin. | parent bioproject:PRJNA1006653 | pubmed:39747457 | Hmga1a overexpression sample 2 | GSM7717536 | source name:adult heart|tissue:adult heart|genotype 1:cmlc2:dsred|genotype 2:Hmga1a overexpression|cell type:cardiomyocytes|treatment:14 days post tamoxifen|geo loc name:missing|collection date:missing | Hmga1a overexpression sample 2 | FASTQ files were mapped with the STARandGO pipeline https://github.com/anna alemany/VASAseq/blob/main/mapping/map star.sh against the danRer11 ENSEMBL genome with the zebrafish Lawson V4.3.2 annotation. Normalization and downstream analysis were performed in R. Due to low read count samples control 2 and overexpression 1 were excluded from analysis. Using the R package EdgeR differentially expressed genes were obtained FC < 1 or >1 and Pval<0.05. Gene lists were subjected to GO analysis using the online tool DAVID. Assembly: danrer11 Supplementary files format and content: excel file containing edgeR results and GO analysis results Supplementary files format and content: count table spliced transcriptcounts | adult heart | zebrafish were treated with tamoxifen to induce Hmga1a overexpression | Unfixed ventricles were dissociated by Collagenase and TrypLE Express treatment to prepare single cell solutions. | tissue:adult heart|genotype 1:cmlc2:dsred|genotype 2:Hmga1a overexpression|cell type:cardiomyocytes|treatment:14 days post tamoxifen | GSM7717536 | GSM7717536: Hmga1a overexpression sample 2; Danio rerio; RNA Seq | GSM7717536 r1 | GSM7717536 | 1 | Unfixed ventricles were dissociated by Collagenase and TrypLE Express treatment to prepare single cell solutions. | RNA-Seq | TRANSCRIPTOMIC | cDNA | SINGLE | ILLUMINA | NextSeq 500 | SRP455779 | HUB-PN-b004_HHHK2BGXN_S1_L004_OE2_cbc.fastq.gz | fastq | 418311900.0 | 6971865.0 | GSM7717536 r4 | 0:60 | A:121375806;C:87324728;G:89011817;T:120559021;N:40528 | 60 | 121375806 | 87324728 | 89011817 | 120559021 | 40528 | SRX21410745 | SRS18649227 | SRA1695358 | Jeroen Bakkers, Hubrecht Institute | Jeroen Bakkers, Hubrecht Institute | 1 | 0.90583 | 0.06349 | 0.87156 | 0.36876 | 60 | B | usable mapping rate | illumina | nextseq | unknown | cdna_unspecified | unknown | sc_generic | bulk | bulk | Netherlands | 2023-08-18 | Adult | Adult | Heart | Cardiovascular System |