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Developing Heart Atlas Established Using Gene Expression Profiles, Spatial Imaging

NEW YORK – A research team led by investigators at the University of California, San Diego has assembled a single-cell transcriptomics and spatially informed heart atlas, providing new clues to heart development, heart function, and heart disease.

As they reported in Nature on Wednesday, the researchers relied on a combination of single-cell RNA sequencing and "multiplexed error-robust fluorescence in situ hybridization" (MERFISH) imaging to assess 142,946 individual heart cells isolated from samples collected between nine and 16 weeks after conception, establishing a developing heart cell atlas that spanned 75 new and known cell subpopulations.

"The current study greatly expands on what cell types and states were previously known to exist within the developing human heart," co-first author Elie Farah and co-senior authors Quan Zhu and Neil Chi, all based at UCSD, said in an email, adding that the atlas revealed previously unappreciated cell subpopulations in parts of the heart that were not characterized in the past.

In particular, the investigators described cell types and subtypes falling within cardiovascular lineages involved in cardiac development, morphogenesis, and function, while highlighting new cell populations found in key heart regions such as the heart's cardiac valves and conduction system.

The team's subsequent analyses also made it possible to investigate spatial interactions between neighboring heart cells, including cell-to-cell interactions influencing cardiac development and heart function.

"These detailed findings into the cellular social interactions and specialization of cardiac cell types constructing and remodeling the human heart offer new insights into structural heart diseases and the engineering of complex multicellular tissues for human heart repair," the authors suggested, noting that their results revealed "detailed social interactions among distinct cell types that specialize and organize into cardiac structures crucial for maintaining heart function."

In ventricular cardiomyocyte cells, for example, the atlas revealed previously unrecognized migration signals suspected of contributing to ventricular wall formation during cardiac morphogenesis and remodeling.

Farah, Zhu, and Chi further suggested that "[i]nformation and insights from our high-resolution molecular and spatial cardiac cell atlas may be used in the future to understand the pathologic mechanisms underlying congenital heart disease (CHD) and adult structural heart diseases, and to develop biologically relevant engineered cardiac organoids and tissues to be used as a platform for drug screening and cardiac regenerative therapies."