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What cell programs mark ischemic cardiomyopathy?

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snRNA-seq of ~100k cardiac nuclei showed fewer cardiomyocytes and more specialized endothelial states in ICM, overlapping other end-stage cardiomyopathy programs.

Source

Single-nucleus RNA sequencing in ischemic cardiomyopathy reveals common transcriptional profile underlying end-stage heart failure

Simonson B, Chaffin M, Hill MC, et al. · Cell reports · 2023

doi.org/10.1016/j.celrep.2023.112086Read the full paper ↗93 citationscc by

Study at a glance

Design
Case-control — snRNA-seq of non-infarct LV from ICM transplant recipients vs NF controls
N
N=15 · 7 ICM + 8 NF; 99,684 nuclei after QC
Population
Human LV nuclei from ICM and non-failing hearts
Outcome
Cell-composition and transcriptional differences in ICM vs NF

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Profiled non-infarct LV nuclei from ICM transplant recipients and non-failing controls with snRNA-seq.

What they found

99,684 QC nuclei in 16 clusters. ICM had fewer cardiomyocytes and more lymphatic/angiogenic/arterial endothelial cells; transcriptional changes resembled HCM/DCM datasets.

The limits

What it doesn't show

End-stage transplant tissue may not represent early ICM; composition shifts are associative.

Key terms

snRNA-seq
Single-nucleus RNA sequencing.
Ischemic cardiomyopathy
Heart failure after ischemic injury/remodeling.
Non-failing control
Comparison hearts without end-stage failure.
Endothelial subtypes
Lymphatic, angiogenic, arterial EC states.
LAMININ signaling
ECM pathway highlighted from endothelium.
Druggable genes
Shared cardiomyopathy targets suggested by dataset mining.

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QC nuclei ~

Common questions

Nuclei after QC?

99,684.

Donors?

7 ICM + 8 NF.

Composition shift?

Fewer cardiomyocytes; more specialized ECs.

Cross-disease?

Similar to HCM/DCM programs.

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