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Sameeksha Tiwari, PhD



Job Title

Postdoctoral Research Fellow

Academic Rank

Research Fellow


Anesthesiology, Perioperative and Pain Medicine


Sameeksha Tiwari, Daniel M. DeLaughter, Azam M. Yazdani, Joshua M. Gorham, Sary F. Aranki, Christine E. Seidman, Jon G. Seidman, Jochen D. Muehlschlegel

Principal Investigator

Jochen D. Muehlschlegel

Research Category: Cardiovascular, Diabetes, and Metabolic Disorders


Ischemic response in the Human Left Ventricle at a single-cell level

Scientific Abstract

Background: Ischemic heart disease is the leading cause of mortality worldwide and the costliest disease in the US. Single-cell RNA sequencing provides an in-depth view of the variations in the cellular response to ischemia, and cellular and molecular changes within cells and allows for the identification of biomarkers and therapeutic targets.

Methods: sc-RNA seq data of eight human LV samples from both baseline and post-ischemia conditions were analyzed. Human Cell Atlas was the reference database for cell type annotation, and the Wilcoxon rank sum test was implemented for differential expression analysis.

Results: The cell type identification resulted in nine distinct cell types. Differential expression of genes revealed RYR2 and TTN as highly expressed cardiomyocyte marker genes, upregulated in the majority of post-ischemic samples with a significant log fold change as well as p-value as compared to baseline. NEGR1 and ABCA8 genes were upregulated in fibroblast cells during post-ischemic conditions.

Conclusions: The gene expression data revealed transcriptional and cellular heterogeneity. Ventricular cardiomyocytes are the most prevalent cardiac cells and have a major share. The upregulation of genes expressed in fibroblast during post-ischemic conditions reflects its significant role in supporting cardiomyocytes’ response to disease.

Lay Abstract

Ischemic heart disease is the condition developed due to inadequate blood supply to heart caused due to blockage of the blood vessels supplying blood to the heart muscle. It is the costliest disease to the US healthcare and the leading cause of mortality worldwide. There is a severe need for an improved mechanistic understanding of ischemic heart disease pathogenesis, the identification of novel targets and innovative strategies to deliver therapies. Single cell transcriptomics represents a powerful to understand the pathogenesis of ischemic heart disease. Single cell RNA-seq analysis is used to understand the transcriptional changes specific to single-cell level and getting a better understanding of complex disease mechanisms. Eight human left ventricle samples from baseline and post ischemia conditions were analyzed. Analysis of cellular heterogeneity enabled the identification of marker genes belonging to distinct cell types and showed significant expression level in pre as well as post ischemic condition. It provides insight into the perturbations of ischemia on gene transcripts expressed in heart tissue.

Clinical Implications

The differentially expressed genes present in ventricular cardiomyocytes, fibroblasts, endothelial cells and their expression in both baseline and post disease samples, provide a basis for understanding their role as therapeutic targets and biomarkers of ischemic heart disease.