Abstract 16650: Transcriptional Profiling of Single Human Heart Cells Reveals Subtypes of Ventricular Cardiomyocytes
Regenerative strategies have the potential to transform the treatment of heart failure. Their success relies on a detailed molecular-genetic understanding of human cardiac cell development. Single-cell deep RNA-sequencing reveals the transcriptional activity of genes, alleviates cell-averaging effects inherent to bulk RNA-sequencing, and enables the discovery of cellular sub-types.
We investigated the transcriptional profiles of 423 single heart cells collected from 18 patients (age range 8 days to 18 years). Comparison with bulk approaches revealed that cardiac genes are highly expressed in our cells and a subset of cells is significantly associated with heart tissue. Focusing on cardiomyocytes (CMs), defined using marker gene expression, we found that genes related to major cardiac transcriptional programs like muscle contraction, muscle cell differentiation, sarcomere organization and energy metabolism, exhibited high variability in their expression. Principle component analysis on highly variable genes followed by clustering yielded distinct groups of similar cells, some with transcriptional hallmarks of known cardiac cell-types and others as-yet-uncharacterized. Finally, we profiled CMs derived from human induced pluripotent (hiPS) cells and preliminary observations suggest a distinct signature from human primary CMs.
With this first map of single human primary heart cells, we hope to provide a resource that aids cardiovascular research and sheds light on the uncharacterized transcriptional heterogeneity of cardiac cells. Using this reference system for precisely positioning hiPS-derived CMs relative to primary human CMs and their sub-types, we can now start to develop molecular strategies for advancing the differentiation of hiPS-derived cells into CMs.
Author Disclosures: A. Bais: None. N. Ammanamanchi: None. J. Spaethling: None. S. Choudhury: None. H. Liu: None. M. Khaladkar: None. J.D. Mich-Basso: None. S.A. Fisher: None. J. Kim: None. J. Eberwine: None. D. Kostka: None. B. Kühn: None.
- © 2016 by American Heart Association, Inc.