biostudies-arrayexpressEmre Taylan DumanHomo sapienshttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-16232Cardiac autonomic neurons control cardiac contractility. Dysregulation of the autonomic nervous system can lead to sympathetic overdrive resulting in heart failure and an increased incidence of fatal arrhythmias. Here, we introduce innervated engineered human myocardium (iEHM), a novel model of neuro-cardiac junctions, constructed by fusion of a bioengineered neural organoid patterned to autonomic nervous system (SNO) and engineered human myocardium (EHM). Projections of sympathetic neurons into EHM formed presynaptic terminals in close proximity to cardiomyocytes and the extensive vascular network co-developing in the tissues. Contractile responses to optogenetic stimulation of the accordingly engineered neuronal component demonstrated functionality of the engineered neuro-cardiac junctions. Modeling long-QT 2 related to KCNH2 mutations in iEHM revealed early afterdepolarizations and autonomic neuron hyperactivity, suggesting a contribution of the autonomic nervous system to hERG-channel dysfunction-related arrhythmias. Collectively, our data demonstrate the utility of iEHM in the delineation of neuron-cardiomyocyte crosstalk at the tissue level and may serve as an important step towards the engineering a human brain-to-heart axis in a dish.biostudies-arrayexpressSample Collection - Tissues were placed in 2 mL collection tube and were washed twice with PBS. Tissues were directly put into liquid nitrogen to be snap frozen.Sequencing - cDNA libraries were sequenced by using an S2 flow cell NovaSeq6000; 100 cycles, 20-25 Mio reads/sample.Sample Treatment - No treatments were given to the tissues.Nucleic Acid Extraction - RNA from frozen tissues were harvested using the Promega ReliaPrep RNA Tissue Miniprep system and was cleaned with the RNA Clean & Concentrator.Growth Protocol - Day 40 SNO and day 28 EHM were fused for 6 weeks generating the iEHM which was supplemented with a 1:1 mixture of Basal medium and EHM medium. Individual EHM and SNO were also cultured individually with the iEHM 1:1 media for the same duration as the iEHM.Library Construction - RNA quality was assessed by measuring the RNA integrity number (RIN) using a Fragment Analyzer HS Total RNA Kit (Advanced Analytical Technologies, Inc.). Library preparation for RNA-Seq was performed in the STAR Hamilton NGS automation using the Illumina Stranded mRNA Prep (Cat.N° 20040534) and the ID for Illumina RNA UD Indexes Set A, Ligation with 96 Indexes (Cat. N° 20091646) starting from 300 ng of total RNA. The size range of the final cDNA libraries was determined by applying the SS NGS Fragment 1- to 6000-bp Kit on the Fragment Analyzer (average 340 bp). Accurate quantification of cDNA libraries was performed by using the DeNovix DS-Series System.OrganizationMINSEQE ScoreAssays and DataProcessed DataMAGE-TAB FilesSequence Alignment - Reads were aligned to the human reference genome (GRCh38) using STAR aligner v2.7.10 and annotated with the Ensembl GTF file (release 110).Data Transformation - Gene-level counts were summarized with featureCounts v1.6.3, and transcript-based counts were normalized using the DESeq2 R package. Pairwise differential gene expression analysis was performed in DESeq2, applying Benjamini-Hochberg multiple testing correction.MetabolomicsUnknownTranscriptomicsGenomicsProteomicsIllumina NovaSeq 6000RNA-seq of coding RNAHomo sapiensMarie-Kristin SchreiberEmre Taylan DumanfalseBioengineering of a human innervated cardiac muscle modelCardiac autonomic neurons control cardiac contractility. Dysregulation of the autonomic nervous system can lead to sympathetic overdrive resulting in heart failure and an increased incidence of fatal arrhythmias. Here, we introduce innervated engineered human myocardium (iEHM), a novel model of neuro-cardiac junctions, constructed by fusion of a bioengineered neural organoid patterned to autonomic nervous system (SNO) and engineered human myocardium (EHM). Projections of sympathetic neurons into EHM formed presynaptic terminals in close proximity to cardiomyocytes and the extensive vascular network co-developing in the tissues. Contractile responses to optogenetic stimulation of the accordingly engineered neuronal component demonstrated functionality of the engineered neuro-cardiac junctions. Modeling long-QT 2 related to KCNH2 mutations in iEHM revealed early afterdepolarizations and autonomic neuron hyperactivity, suggesting a contribution of the autonomic nervous system to hERG-channel dysfunction-related arrhythmias. Collectively, our data demonstrate the utility of iEHM in the delineation of neuron-cardiomyocyte crosstalk at the tissue level and may serve as an important step towards the engineering a human brain-to-heart axis in a dish.2026-05-11T00:00:00Z2026-05-13T14:10:56.413Z2025-11-20T14:33:16.058ZE-MTAB-16232ERP185423EFO_0002944EFO_0004170EFO_0003789EFO_0004917EFO_0005518EFO_0003816EFO_0003738EFO_0004184EFO_0003969