Haematopoietic loss of KDM6A impairs cardiac recovery in heart failure via epigenetic reprogramming of myeloid cells (scATAC-SEQ)

ABSTRACT: 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

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: David John 

PROVIDER: E-MTAB-17569 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress