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The Research Institute at Nationwide Children's Hospital Genetics of Congenital Heart Disease (CHD)

ABSTRACT: The Research Institute at Nationwide Children's Hospital Genetics of Congenital Heart Disease (CHD)

PROVIDER: PRJNA625349 | ENA |

REPOSITORIES: ENA

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The Research Institute at Nationwide Children's Hospital Genetics of Congenital Heart Disease (CHD)

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Project description:The heart, the first organ to develop, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of CHD patients survive into adulthood but often suffer premature death from heart failure (HF) and non-cardiac causes 1. To gain insight into poorly understood disease progression, we performed single nuclear RNA sequencing (snRNA-seq) and analyzed more than 157,000 nuclei from donors and CHD patients, including hypoplastic left heart syndrome (HLHS) and Tetralogy of Fallot (TOF), two common forms of cyanotic CHD lesions, as well as, dilated (DCM) and hypertrophic (HCM) cardiomyopathies. We observed CHD specific cell states in cardiomyocytes (CMs) which had evidence of insulin resistance and increased FOXO and CRIM1 expression. Cardiac fibroblasts (CFs) in HLHS had enrichment for a low HIPPO and high YAP cell state characteristic of activated CFs. Imaging Mass Cytometry (IMC) uncovered the spatially resolved perivascular microenvironment consistent with an immunodeficient state in CHD. Peripheral immune cell profiling suggested deficient monocytic immunity in CHD in agreement with CHD predilection to infection and cancer 2. Our comprehensive CHD phenotyping provides a roadmap for future personalized medicine in CHD.

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