Pathogenic LMNA variation disrupts a tissue-specific lamina-chromatin signature, resulting in loss of cellular identity

We demonstrate that a normal function of lamina-associated chromatin is to maintain silencing of undesired lineages, and laminopathies, like LMNA T10I and R541C, may specifically target these regions, resulting in predictable tissue-specific nuclear architecture changes during development. Mapping of LB1 and H3K9me2 domains in control and LMNA T10I iPSC-derived cardiac myocytes at day 25 and 45 post-differentiation; mapping of LB1 and H3K9me2 domain in control and LMNA R541C iPSC-derived cardiac myocytes; mapping LB1 and H3K9me2 domains in control, LMNA T10I, and R541C iPSC-derived hepatocytes; mapping LB1 and H3K9me2 domains in control, LMNA T10I, and R541C iPSC-derived adipocytes; RNAseq of d25 control, T10I, and R541C iPSC-derived cardiac myocytes; RNAseq of control, T10I, and R541C iPSC-derived adipocytes.