{"database": "metadata", "table": "run_metadata", "rows": [[25262, "SRR25723815", "SRX21447925", "SRS18684547", "SRP456323", "PRJNA1008049", "Interspecies comparison reveals Hmga1 as driver of cardiac regeneration [scRNA seq]", "GSE241390", "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", null, "hmga1a mutant plate 1", "GSM7728118", null, "source name:adult heart|tissue:adult heart|genotype:nppa:mCitrine|genotype:hmga1a mutant|cell type:border z1 cardiomyocytes|treatment:7 days post cryoinjury|geo loc name:missing|collection date:missing", "hmga1a mutant plate 1", "Based on the distribution of the log10 total reads plotted against the frequency  we introduced a cutoff at minimally 600 reads per cell to be included for further analysis which left us with a total of 1310 cells 653 wildtype and 657 hmga1a /  cells. Next  single cell data was analyzed using Seurat 81. Using the following parameters: Variable features = all genes  dimensions = 8  resolution = 0.7. This resulted in the identification of 6 clusters which were plotted in a two dimensional UMAP. Monocle2 was used to identify genes that were differentially expressed over pseudo time and organized in a self organizing map with of 8 modules. Pseudo temporal values assigned to single cells were integrated in our Seurat object and the pseudo temporal ordering was plotted on the UMAP. DAVID was used to perform GO analysis for the 8 modules. Assembly: danrer9 Supplementary files format and content: excel file containing pseudotime modules and their  genes and GO terms per module Supplementary files format and content: count tables transcriptcounts", "adult heart", "cryoinjury was performed 7 days before hearts were extracted", "Unfixed ventricles were dissociated by Collagenase and TrypLE Express treatment to prepare single cell solutions. Cells were subsequently FACS sorted based on nppa:mCitrine expression in 384 well plates  each well containing 1 cell  containing Vapor Lock oil with CEL Seq2 barcoded primers  spike in mRNA and dNTPs Single Cell Discoveries. Plates were spun down and frozen at  80oC until ready for library prep. Single cell sequencing libraries were prepared by Single Cell Discoveries Utrecht  The Netherlands using the SORT seq protocol . The CEL Seq2 protocol was used for library prep Hashimshony et al.  2016. Illumina sequencing libraries were prepared with the TruSeq small RNA primers Illumina and paired end sequenced at 75 bp read length on the Illumina NextSeq platform. In total seven 384 well plates were sequenced containing one cell per well of which three were obtained from wildtype cells and four from hmga1a mutant cells.", null, "tissue:adult heart|genotype:nppa:mCitrine|genotype:hmga1a mutant|cell type:border z1 cardiomyocytes|treatment:7 days post cryoinjury", "GSM7728118", "GSM7728118: hmga1a mutant plate 1; Danio rerio; RNA Seq", "GSM7728118 r1", "GSM7728118", "1", "Unfixed ventricles were dissociated by Collagenase and TrypLE Express treatment to prepare single cell solutions. Cells were subsequently FACS sorted based on nppa:mCitrine expression in 384 well plates  each well containing 1 cell  containing Vapor Lock oil with CEL Seq2 barcoded primers  spike in mRNA and dNTPs Single Cell Discoveries. Plates were spun down and frozen at  80oC until ready for library prep. Single cell sequencing libraries were prepared by Single Cell Discoveries Utrecht  The Netherlands using the SORT seq protocol . The CEL Seq2 protocol was used for library prep Hashimshony et al.  2016. Illumina sequencing libraries were prepared with the TruSeq small RNA primers Illumina and paired end sequenced at 75 bp read length on the Illumina NextSeq platform. In total seven 384 well plates were sequenced containing one cell per well of which three were obtained from wildtype cells and four from hmga1a mutant cells.", null, "RNA-Seq", "TRANSCRIPTOMIC SINGLE CELL", "cDNA", "PAIRED", "ILLUMINA", "NextSeq 500", null, "SRP456323", null, null, "HUB-DB-003_AHVKTGBGX7_S6_L004_R1_001.fastq.gz HUB-DB-003_AHVKTGBGX7_S6_L004_R2_001.fastq.gz", "fastq fastq", 414000732.0, 4813962.0, "GSM7728118 r4", "0:26 1:60", "A:112224009;C:76213738;G:80259829;T:145201785;N:101371", 26, 60, null, null, 112224009, 76213738, 80259829, 145201785, 101371, "SRX21447925", "SRS18684547", "SRA1698978", "Jeroen Bakkers, Hubrecht Institute", "Jeroen Bakkers, Hubrecht Institute", 2, 0.10103, 0.71981, 0.09294, 0.25413, 0.98902, 0.93669, 0.52994, 0.51172, 26, 60, "T", "B", "sc-like readlen", "illumina", "nextseq", "unknown", "small_rna", "trueseq", "sc", "single_cell_plate", "celseq", null, "Netherlands", "2023-08-22", "Adult", "Adult", "Heart", "Cardiovascular System"]], "columns": ["rowid", "run.accession", "experiment.accession", "sample.accession", "study.accession", "bioproject", "study.title", "study.alias", "study.type", "study.abstract", "study.attributes", "study.PMIDs", "sample.description", "sample.title", "sample.alias", "sample.centername", "sample.attributes", "GEOsample.title", "GEOsample.dataprocessing", "GEOsample.source", "GEOsample.treatmentprotocol", "GEOsample.extractprotocol", "GEOsample.growthprotocol", "GEOsample.characteristics", "GEOsample.accession", "experiment.title", "experiment.alias", "experiment.library_name", "experiment.design_description", "experiment.library_construction_protocol", "experiment.attributes", "experiment.library_strategy", "experiment.library_source", "experiment.library_selection", "experiment.library_layout", "experiment.platform", "experiment.instrument_model", "experiment.spot_descriptor", "experiment.study_ref", "run.title", "run.attributes", "run.filename", "run.semantic_name", "run.total_bases", "run.total_spots", "run.alias", "run.read_lengths", "run.base_counts", "run.r1_length", "run.r2_length", "run.r3_length", "run.r4_length", "run.Acount", "run.Ccount", "run.Gcount", "run.Tcount", "run.Ncount", "run.experiment", "run.pool_member", "submission.accession", "submission.srasource", "submission.bioprojectsource", "seqdetective.n_mates", "seqdetective.mapping_rate.mate1", "seqdetective.mapping_rate.mate2", "seqdetective.nofeature_rate.mate1", "seqdetective.nofeature_rate.mate2", "seqdetective.sparsity.mate1", "seqdetective.sparsity.mate2", "seqdetective.pos_strand_rate.mate1", "seqdetective.pos_strand_rate.mate2", "seqdetective.readlen.mate1", "seqdetective.readlen.mate2", "seqdetective.judgement.mate1", "seqdetective.judgement.mate2", "seqdetective.judgement.reason", "platform_family", "instrument_generation", "read_bias", "selection_class", "prep_kit", "sc_or_bulk", "tech_class", "technology", "tech_variant", "submission.bioprojectsource.country", "earliest_date", "devstage_curation", "devstage_curation_coarse", "tissue_curation", "tissue_curation_coarse"], "primary_keys": ["rowid"], "primary_key_values": ["25262"], "units": {}, "query_ms": 9.019482000439893}