Researchers from the KTH Royal Institute of Technology have unveiled a groundbreaking fetal heart map that combines spatial and single-cell transcriptomics with imaging data from 36 hearts. This extensive effort has resulted in what they describe as the “most comprehensive spatiotemporal atlas” of human heart development during the first trimester, detailed in a recent article published in Nature Genetics.
The study outlines the formation and interaction of various cell groups in the developing heart, particularly during the late first and early second trimesters. According to Enikő Lázár, MD, PhD, a postdoctoral researcher at KTH and one of the lead authors, the research illustrates how essential components of the heart—such as the pacemaker system, heart valves, and septum—develop and function.
This knowledge is expected to enhance prenatal care and could pave the way for innovative therapies targeting congenital defects, such as septal defects or valve malformations, which often arise in early development.
Among the significant discoveries made in this research is a newly identified group of adrenaline-producing cells, likely unique to humans. Lázár notes that these “neuroendocrine chromaffin” cells may enable the heart to effectively respond to low oxygen levels during fetal development or at birth. They might also play a role in how the fetal heart manages stress and suggest a possible cellular origin for rare heart tumors known as cardiac pheochromocytomas.
The map has also revealed a rich diversity of cells constituting the heart valves and atrial septum, offering insights into the formation of the heart”s internal structures and the reasons behind congenital defects like valve malformations. Furthermore, the researchers identified various mesenchymal cells that support the structural formation of the fetal heart, which could be implicated in conditions such as valve defects or arrhythmias.
This comprehensive atlas also details the intricate wiring of cells that constitute the heart”s natural pacemaker and conduction system, including the sinoatrial node and Purkinje fibers. The study illustrates how nerve and support cells integrate into the heart and interact with pacemaker cells, highlighting the early influence of different neurotransmitters on heart development.
While the findings are promising, the researchers acknowledge the limitations of their study, which did not encompass the initial two weeks of cardiogenesis, a period when many genes associated with congenital heart diseases are already active. They suggest that an increased sample size could enhance the robustness and resolution of their analysis and advocate for the integration of multiomics data to enrich the understanding of cardiogenesis.
To facilitate further research, the team has made their findings accessible via an interactive online tool, which could provide additional insights into early cardiogenesis and serve as a reference for gene expression patterns linked to congenital heart diseases, as well as for evaluating human pluripotent stem cell-derived cardiac models.
