MYL4 identifies intramural anatomy of Purkinje fibers in human hearts
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ABSTRACT:
PROVIDER: PRJNA1234208 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32636900_1.fastq.gz | Fastqsanger.gz | |||
| SRR32636900_2.fastq.gz | Fastqsanger.gz | |||
| SRR32636901_1.fastq.gz | Fastqsanger.gz | |||
| SRR32636901_2.fastq.gz | Fastqsanger.gz | |||
| SRR32636902_1.fastq.gz | Fastqsanger.gz |
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Project description:ABSTRACTBACKGROUND: Cardiac Purkinje fibers (PFs) orchestrate myocardial synchrony but in regions of myocardial scarring driver ventricular arrhythmia. It is hypothesized that arrhythmias refractory to ablation may be driven by PFs deep in the scarred myocardium. However, knowledge of human PF anatomy remains reliant on data generated in animal models, obscuring understanding of the substrate underpinning dysrhythmia and pacing strategies. OBJECTIVES: Establish and utilize a human biomarker to delineate PF anatomy in humans. METHODS: RNA-sequencing and differential expression analysis of transcriptomes from human hearts (n=10) revealed 99 genes upregulated in PFs versus ventricular myocardium and endocardium. Whole mount megablock cross sectional analysis was performed with cardiac troponin, MYL4, PAS, Masson’s Trichrome, pro-ANP, and GJA5 colocalization. RESULTS: Comparative transcriptomics from human hearts (n=10) identified Myosin light chain 4 (MYL4) as a promising human PF marker for distinguishing conductive from contractile myocardium. Using PF rich bundle branch and subendocardial regions, MYL4 specificity was validated using canonical PF markers in human (n=3), dog (n=3), goat (n=3), and pig (n=3) hearts. Cross sectional histology of the entire human ventricular myocardium uncovered a deep seeded network of transmurally intercalated, MYL4 positive PFs. This previously unrecognized distribution of the cardiac conduction system accounted for over 60% of human myocardial PF content. CONCLUSIONS: Such significant intramural prevalence exposes limitations associated with treatment approaches based on dogma that PF anatomy is restricted to subendocardium. MYL4 here enabled a comprehensive visualization of human cardiac conduction system, offering an intricate bioanatomical map for heart rhythm management.
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Project description:Purkinje fibers form a network of specializedventricularmyocardial cells to assure a coordinatedpropagation of the electrical impulseduring normalforheartefficientcontractionof the heart.Thedevelopmental origins of Purkinje fibers and their roles during cardiac arrhythmia have been reported.However, theresponse of Purkinje fibers to ischemic injury and theirfunctionrolesduring myocardialregenerationare still illusive. Here we introduceda novel inducibleCreallelemouse linethat specificallylabelsthemousecardiac conduction system. Fate mappingshowed Cre activity in different componentsofindicatedspecific labeling ofthe cardiac conduction system, including the sinoatrial and atrioventricularnodes,as well as the Purkinje fibersdifferentknown and unknowncomponents ofthecardiac conductionsystem. RNA-Seqof laser-captured Purkinje fibers showed a uniqueinjuryresponse occurredafterischemic injuryin thisventricularpart of the conductionsystemand corresponding changes in.Ccellularcompositionchange inofPurkinje fibersafter ischemic injury waswereobserved using immunostaining
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Project description:We performed gene-expression analysis of mouse Purkinje cells as a model M-bM-^@M-^\single-type neuronM-bM-^@M-^]. DNA microarray analysis detected at least 7,055 genes in Purkinje cells, most of which are classified into functional molecule categories. Our comparative analysis between Purkinje cells and the granule cell layer showed that the characteristic expression pattern in Purkinje cells was particularly represented by M-bM-^@M-^\the neural communication systemM-bM-^@M-^] components. Pukinje cells and granule cell layer of the mouse cerebellum were collected by laser microdissection for RNA extraction and hybridization on Affymetrix microarrays.
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2009-03-20 | GSE15311 | GEO
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