{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307910/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307910"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Nuclear envelope rupture in cardiomyocytes orchestrates early transcriptomic changes and immune activation in LMNA-DCM that are reversed by LINC complex disruption","description":"Mutations in the LMNA gene, which encodes the nuclear envelope (NE) proteins lamins A/C, cause dilated cardiomyopathy (LMNA-DCM) and other diseases. The pathogenic mechanisms for LMNA-DCM remain poorly understood, limiting current treatment options and leading to high mortality amongst patients. We developed a mouse model with inducible, cardiomyocyte-specific Lmna deletion and performed comprehensive transcriptomic analyses (bulk, single-nucleus, and spatial) across disease progression. We identified key disease-driving genes involved in cellular responses to DNA damage, cytosolic pattern recognition receptor signaling, and innate immunity that originated from two disease-specific cardiomyocyte subpopulations. Spatial mapping revealed aberrant interactions between these cardiomyocytes, fibroblasts, and immune cells, contributing to tissue-wide transcriptional changes. Using mice with inducible, cardiomyocyte-specific disruption of the LINC complex, which transmits cytoskeletal forces to the nucleus, we demonstrated that reducing NE rupture corrected ~50% of misregulated genes and dramatically improved cardiac function and survival in the LMNA-DCM mouse model. These findings suggest that loss of nuclear integrity in Lmna-depleted cardiomyocytes triggers cytosolic DNA sensing and maladaptive cell-cell communication with fibroblasts and immune cells, promoting fibrosis and inflammation characteristic of LMNA-DCM.","dates":{"publication":"2026/09/08"},"accession":"GSE307910","cross_references":{"GSM":["GSM9233803","GSM9233802","GSM9233805","GSM9233804"],"GPL":["34290"],"GSE":["307910"],"taxon":["Mus musculus"]}}