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The cytoskeleton drives abnormal chromatin-lamina interactions in LMNA-deficient cardiomyocytes.

GSE300197 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 30 samples Submitted 2026/03/26 Platform GPL18573Platform GPL30882
Summary
Spatial organization of chromatin at the nuclear lamina is critical for cellular identity, but mechanisms governing genome-lamina interactions remain unresolved. In particular, it remains unclear if and how mechanical inputs impact genome-lamina interactions. We modeled aspects of laminopathies via siRNA-mediated lamin A/C (LMNA) knockdown to examine how the nuclear lamina and cytoskeleton contribute to loss of lamina-associated domain (LAD) organization. Genomics and imaging analyses reveal spatial positioning of LADs with a specific molecular signature are particularly vulnerable to LMNA reduction. Further, a subset of these LADs retain their lamina-association with either concomitant disruption of the Linker of Nucleoskeleton and Cytoskeleton complex or microtubule depolymerization. Conversely, microtubule stabilization phenocopies spatial positioning changes observed in LMNA-knockdown cells. These data suggest peripheral chromatin organization is regulated by the balance of nuclear lamina and cytoskeletal interactions across the nuclear membrane. In the context of a compromised nuclear lamina, such as LMNA reduction, the cytoskeleton contributes to loss of peripheral chromatin organization.
Published in
The cytoskeleton contributes to abnormal genome-lamina interactions in LMNA-deficient cardiomyocytes
Shen KM, Shields EJ, Barka V et al. · The Journal of cell biology 2026 · PMID 41891953 · doi:10.1083/jcb.202506137
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Direct links to NCBI, no account and no request form: the whole study as GSE300197_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 30 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1279218 and SRA study SRP593002. Searching any of these in the dataset finder brings you back here.

Study design
11 conditions, mostly in duplicate
hiPSC, siScr mCh, LMNB1, ×3 hiPSC, siLMNA mCh, LMNB1, ×3 hiPSC, siLMNA DNKASH, LMNB1, ×3 hiPSC, siScr DNKASH, LMNB1 ×3 hiPSC, siScr mCh, rep1, tech ×2 hiPSC, siScr mCh, rep2, tech ×2 hiPSC, siScr mCh, rep3, tech ×2 hiPSC, siLMNA mCh, rep1, tech ×2 +7 more

Supports a between-group comparison across 26 samples.

11 replicated groups read from 30 sample titles; they account for 26 of them. Check it against the sample list below before relying on it.

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