217-HMGN1 Dosage Drives Down Syndrome Cardiac Defects

Paper Talk · Nov 8, 2025 · 17m

This article presents research identifying a key genetic contributor to congenital heart defects (CHDs) associated with Down syndrome, or trisomy 21. Using human induced pluripotent stem cells (hiPSCs) and a mouse model of Down syndrome, the authors investigated dosage-sensitive genes on chromosome 21 that disrupt heart development, specifically focusing on the atrioventricular canal (AVC) defects. Through single-cell RNA sequencing (scRNA-seq) and a CRISPR-activation (CRISPRa) screen, the study isolates the epigenetic regulator HMGN1 as the critical gene whose triplication causes AVC…