Journal of Cell Signaling
Open Access

Single-Cell RNA Sequencing: Examining Transcriptomic Characteristics and Cellular Interactions in Neonatal Cardiac Development

Tambuwala Murtaza^{* *}Correspondence: Tambuwala Murtaza, Department of Pharmacy and Pharmaceutical Science, Ulster University, Coleraine, UK, Email:

Author info »

Description

The heart is the first organ to form during embryonic development, playing an important role in delivering oxygenated blood to the embryo. This process is essential for the maturation of the vasculature and the formation of other organs. Cardiac cell specification and maturation are influenced by various factors, including epigenetic mechanisms (e.g., DNA methylation), transcription factors (e.g., GATA-Binding Protein 4 (GATA4), Mesoderm Posterior BHLH Transcription Factor 1(MESP1), Tbox Transcription Factor (TBX), NK2 Homeobox 5 (NKX2.5) and morphogens (e.g., Transforming Growth Factor-Beta (TGF- β), Bone Morphogenetic Protein 4 (BMP4), Fibroblast Growth Factor (FGF). These factors, through their influence on transcriptional programs, give rise to the diverse cell types of the heart. The development of the heart involves a range of cell types, including endothelial cells, cardiomyocytes, immune cells and fibroblasts. Interactions between these cell lineages are essential for forming and maturing the mammalian heart, transitioning from a linear tube to a fully formed four-chambered structure. Due to its intricate topography, visualizing heart development is key to understanding the process. Transcriptional regulation plays an important role in this process. However, the transcriptomes of human embryonic hearts remain largely unexplored, primarily because conventional transcriptome analyses cannot resolve the various cell populations in the heart. Recent advancements in high-throughput sequencing technologies, particularly Single-Cell Ribo Nucleic Acid Sequencing (scRNA-seq), now allow for detailed exploration of cellular heterogeneity in the developing human heart. These techniques enable a deeper understanding of cardiac differentiation.

Comprehensive spatial and cellular heterogeneity analysis of the developing human heart at three key stages of the first trimester: 4.5-5, 6.5 and 9 Post-Conception Weeks (PCW), using spatial transcriptomics and scRNA-seq. However, further research covering additional time points is necessary. Used scRNA-seq to profile the gene expression of 4,000 cardiac cells from human embryos, identifying four major cell types: Cardiomyocytes, valvar interstitial cells, endothelial cells and cardiac fibroblasts. Despite the insightful findings, this study’s limited cell types and sample size warrant further investigation examined fetal human heart single-cell transcriptomes from mid-gestational healthy (19-22 weeks) and anti-SSA/Ro-associated Congenital Heart Block (CHB) samples (21 weeks), providing additional insights into cardiac development, employed single-nucleus RNA sequencing to capture transcriptional changes in multiple cardiac cell populations from fetal stages (19 and 20 weeks) to adulthood. However, these studies did not address the significant changes occurring at the early stages of heart development.

In this study, we performed single-cell RNA sequencing on 19,808 cells derived from embryonic heart tissue at four developmental time points. We identified 11 major cell types and various specific clusters within each cell type. Our analysis revealed significant differences in cell composition, gene expression and signaling pathways throughout the development of the human fetal heart. Overall, our study provides a comprehensive and systematic description of gene expression profiles and cellular communication in the developing human heart. These findings will aid in the generation of de novo cardiac cell types and heart organoids, as well as enhance our understanding of disease origins.

Conclusion

In conclusion, this study provides a detailed and systematic analysis of cellular heterogeneity and gene expression during human fetal heart development using single-cell RNA sequencing. By identifying 11 major cell types and revealing key differences in gene expression and signaling pathways, our findings deepen the understanding of cardiac differentiation and maturation. These insights have significant implications for the generating cardiac cell types and heart organoids, as well as the advancing our knowledge of the molecular mechanisms underlying the heart development and disease. Further examination of the additional time points will be essential for more comprehensive understanding of early cardiac development.