Using a combination for spatial, single-cell transcriptomics and imaging data from 36 hearts, scientists from the KTH Royal Institute of Technology and their collaborators have come up with what they describe as the “most comprehensive spatiotemporal atlas of first-trimester human heart development to date.” Full details are provided in a Nature Genetics paper published this week that is titled “Spatiotemporal gene expression and cellular dynamics of the developing human heart.”
Their work provides a blueprint of the developing heart during the late first and early second trimesters that shows how different groups of cells are arranged and interact during fetal development. It shows how “key parts of the heart—like the pacemaker system, heart valves, and the wall between the upper chambers—form and function,” said Enikő Lázár, MD, PhD, postdoctoral researcher in the Department of Gene Technology at KTH Royal Institute of Technology and SciLifeLab and one of the lead authors of the study. Importantly, understanding how the cardiac architecture forms could improve prenatal care as well as lead to new treatments for congenital defects like holes between heart chambers or valve deformities which typically originate during early development.
One of the findings reported in the study was the discovery of a previously unknown group of cells that produce adrenaline. According to Lázár, these cells are likely unique to human beings and may help the heart respond effectively to low oxygen levels during development or birth. These “neuroendocrine chromaffin” cells may play a coordinating role in the fetal heart’s response to stress and indicate a potential cellular origin for cardiac pheochromocytomas, which are rare tumors that originate inside the heart.
Other insights revealed by the map include the diversity of the cells that make up the heart valves and the atrial septum. The diversity offers clues to how the heart’s internal structures form and why congenital defects like valve malformation occur. Additionally, the researchers found that fetal hearts have a variety of supporting cells, or mesenchymal cells, that provide scaffolding to help shape their structure. These cells may also be involved in diseases like valve defects or arrhythmias.
Also identified in the study is the precise wiring of cells that form the heart’s natural pacemaker and conduction system including the sinoatrial node, which sets the heartbeat, and Purkinje fibers, which spread the signal. Their map also traces how nerve cells and support cells grow into the heart and connect with the pacemaker cells, and reveals that different types of neurotransmitters start influencing the heart early during development.
There is room to build on these findings. As the scientists note, “our study is intrinsically constrained by the developmental time frame investigated, which does not cover the first two weeks of cardiogenesis, during which many congenital heart disease-related genes are already active.” Furthermore, “an increased sample size would improve the resolution and robustness of our analysis and enable further validation or refinement of the identified cell populations” and “integrating multiomics data would further enrich the proposed transcriptome-based cellular and architectural framework of cardiogenesis.”
The findings are available through an interactive online tool for scientists seeking deeper insights into how the heart develops. “Our datasets may furnish novel insight into other aspects of early cardiogenesis not covered by our current study,” the researchers wrote “and serve as a spatiotemporal reference for early expression patterns of candidate genes in congenital heart diseases and for benchmarking human pluripotent stem cell-derived cardiac cell and tissue models, often resembling embryonic phenotypes.”
