{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["David John"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-17614"],"description":["Clonal haematopoiesis (CH), the expansion of blood-cell clones carrying acquired mutations, is an independent risk factor for cardiovascular disease. Although mutations in DNMT3A and TET2 are well studied, the cardiovascular consequences of KDM6A mutations remain unclear. KDM6A is an X-linked histone demethylase that is commonly mutated in patients with heart failure. Here, we perform multi-omics profiling and functional characterisation of mouse models and patient-derived data to show that haematopoietic KDM6A loss impairs cardiac recovery after myocardial infarction. KDM6A deficiency increases myeloid-cell recruitment to the injured heart and reprogrammes monocytes, macrophages and neutrophils towards inflammatory, migratory and glycolytic states. Patients with heart failure and KDM6A-dr"],"repository":["biostudies-arrayexpress"],"sample_protocol":["Nucleic Acid Extraction - The sample was then centrifuged at 300g for 10 minutes at room temperature, with acceleration and brakes enabled. The supernatant was discarded, and the pellet was resuspended in 50 mL PBS. Platelets were removed by two additional washing steps and centrifugation at 200g for 10 min and the supernatant was discarded.","Sequencing - The indexed libraries were pooled equimolarly and sequenced on two Illumina NovaSeq 6000 instruments with paired-end sequencing (26×98 bp) at GenomeScan (Leiden, the Netherlands).","Sample Collection - PBMCs were isolated by density gradient centrifugation. Briefly blood was layered on top of human Pancoll (1.077 g ml−1, PAN Biotech), followed by centrifugation at 800g for 20 minutes at room temperature without brakes applied. The white ring of PBMCs was transferred to a new 50 mL Falcon tube, and PBS was added to bring the total volume to 50 mL","Library Construction - Human PBMCs were processed according to the manufacturer's instructions, with cells loaded onto a 10X Chromium Controller (10X Genomics). Human patient samples were screened for additional CH driver mutations. No co-occurring CH driver mutations were detected, ensuring that the patient group used for downstream analyses represented KDM6A-driven CH without detectable additional CH-driver events. The libraries for single-cell RNA sequencing (scRNA-seq) were prepared using the Chromium Single-Cell 3′ v3 Reagent Kit (10X Genomics). Initially, individual cells were isolated into droplets within an emulsion, each containing gel beads coated with unique primers that carried 10X cell barcodes, unique molecular identifiers, and poly(dT) sequences. Reverse transcription then g"],"figure_sub":["Organization","MINSEQE Score","Assays and Data","Processed Data","MAGE-TAB Files"],"data_protocol":["Data Transformation - Filtered matrices were analyzed using Seurat 5.2 in R studio with R 4.4.2. Quality control steps included removing features detected in less than 3 cells and removing cells with less than 200 features, more than 6000 genes and more than 20% mitochondrial RNA. Data was normalized by scaling feature expression by the total expression per cell, multiplied by a scale factor of 10,000 and then log-transformed. This was followed by selection of features that exhibit high cell-to-cell variation and data was linearly transformed prior to dimensionality reduction. Data was subjected to principal component analysis and unsupervised clustering by the Louvain clustering method. The number of PCAs to apply were determined using an ElbowPlot in Seurat. Samples were integrated using","Sequence Alignment - Fastq files were mapped to the human (GRCh38) genome using CellRanger 7.1 (10x Genomics)."],"omics_type":["Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["Illumina NovaSeq 6000"],"study_type":["RNA-seq of coding RNA from single cells"],"species":["Homo sapiens"],"pubmed_authors":["David John"],"additional_accession":[]},"is_claimable":false,"name":"Haematopoietic loss of KDM6A impairs cardiac recovery in heart failure via epigenetic reprogramming of myeloid cells (scRNA Human)","description":"Clonal haematopoiesis (CH), the expansion of blood-cell clones carrying acquired mutations, is an independent risk factor for cardiovascular disease. Although mutations in DNMT3A and TET2 are well studied, the cardiovascular consequences of KDM6A mutations remain unclear. KDM6A is an X-linked histone demethylase that is commonly mutated in patients with heart failure. Here, we perform multi-omics profiling and functional characterisation of mouse models and patient-derived data to show that haematopoietic KDM6A loss impairs cardiac recovery after myocardial infarction. KDM6A deficiency increases myeloid-cell recruitment to the injured heart and reprogrammes monocytes, macrophages and neutrophils towards inflammatory, migratory and glycolytic states. Patients with heart failure and KDM6A-dr","dates":{"release":"2026-08-27T00:00:00Z","modification":"2026-09-07T12:50:25.96Z","creation":"2026-09-07T12:50:03.469Z"},"accession":"E-MTAB-17614","cross_references":{"EFO":["EFO_0002944","EFO_0004170","EFO_0005684","EFO_0004917","EFO_0005518","EFO_0003816","EFO_0004184"]}}