Studying heart samples from patients with cardiomyopathies, as well as from controls without heart disease, researchers have provided new insights into the cellular and molecular biology of human heart failure – a highly fatal condition that affects 23 million people worldwide.
These results – which leveraged a technique called single-nucleus RNA-sequencing (snRNAseq) analysis – “upend a prevalent dogma that heart failure results from a common final pathway,” say the study’s authors, “and can guide the future development of therapies with selective targets to enhance personalized medicine.
” Cardiomyopathy is a group of diseases that affect the heart muscle in ways that interfere with the organ’s ability to pump blood effectively. These serious disorders are major causes of heart failure and leading indications for heart transplantation. Some cardiomyopathies, including dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM), can arise from mutations in genes that encode proteins with diverse functions in cardiac biology.
However, how the pathogenic variants in genes associated with DCM and ACM convey such high risks for the development of heart failure is unknown. While the notion that diverse stimuli converge on a common final pathway to lead to heart failure has been propelled, new technologies provide direct opportunities to evaluate whether, instead, genotype influences disease pathways.
The researchers performed snRNAseq in heart tissue samples from patients with genetic and idiopathic (mutation-negative) DCM and ACM and in those without structural heart disease. Using machine learning to probe the 880,000 transcriptomes the analysis generated, the researchers were able to identify distinct cell types involved in the path towards heart failure and their locations in the heart, as well as genotype-associated pathways, intercellular interactions, and differential gene expression for these disorders at the single-cell resolution.
"This network showed remarkably high prediction of the genotypes for each cardiac sample, thereby reinforcing our conclusion that genotypes activate very specific heart failure pathways,” said the authors.
“Although interrogation of these datasets provides ongoing opportunities for discovery, our findings provided substantial evidence that genotype influenced pathological remodeling of the heart.”
https://www.science.org/doi/10.1126/science.abo1984
How pathogenic gene variants lead to heart failure
- 1,233 views
- Added
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Mature heart muscle cells created in the laboratory from stem cells
Read more
Cell of origin affects malignancy and drug sensitivity of brain tumors
Read more
Protein essential for healthy gut cell development identified!
Read more
Reprogramming of liver cells to pancreas progenitor cells based on…
Read more
The intestine has a reservoir of stem cells that are resistant to c…
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar