Scientists have just published the most detailed map of the developing human heart yet.
The atlas includes 75 types of heart cells, including cell types in heart valves and muscles that power his punches which have never been seen before. It shows how these and other cells organize to form the various internal structures of the heart in the womb. The research, which was published Wednesday (March 13) in the journal Nature also reveals how different cells interact during heart development.
“For the first time, we can see how heart cells organize to form the different structures of the heart in high resolution, similar to zooming in on individual houses on Google Maps.” Eli Farah the first author of the study and a postdoctoral fellow in Neil Chee The research lab at the University of California, San Diego (UCSD) told Live Science in an email.
To draw their map, Farah and his colleagues examined whole human hearts that had been donated to UCSD Perinatal Biorepository , a tissue bank used for human pregnancy research. Hearts in the study were donated between 9 and 16 weeks of fetal development. At this stage, the heart has already progressed beyond a simple tube to develop four separate cameras but it is still much smaller than an adult’s heart.
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One technique the researchers used was single-cell RNA sequencing, which allowed them to look at a type of genetic material called RNA in each heart cell. RNA carries blueprints stored in genes to the cell’s protein-building factories, so analyzing RNA can help scientists identify different types of cells.
The other technique used in this study is called “multiplexed error-stable fluorescence in situ hybridization,” or MERFISH for short. It was introduced in 2019 by Quan Ju , associate director of UCSD’s Center for Epigenomics and co-senior author of the new paper. This method allows researchers to detect and quantify the RNA transcripts—the copied blueprints—of hundreds of genes in each cell while recording the cell’s anatomical location within an organ.
Zhu teamed up with Qi’s lab to use this cutting-edge technology to study how human hearts develop, becoming “the first research team to apply MERFISH technology to study the human developing heart at spatially resolved resolution of one cell,” Zhu told Live Science in an email. In other words, MERFISH allowed the team’s map to capture the characteristics and coordinates of individual cells in the fetal heart.
“Not only are we able to identify unexpected cell types specific to the developing heart that are not found in the adult heart, but we also gain a deeper understanding of why the left side of our hearts is different from the right at a very early stage.” Zhu added. For example, more layers of heart muscle cells were observed in the lower left ventricle or left ventricle than in the right ventricle, indicating that the left ventricle develops earlier than the right.
In addition to analyzing whole hearts, the team conducted genetic studies on mice and laboratory tests with human stem cells. They demonstrated how different types of cells communicate with each other to stimulate the development of the heart’s internal structures.
For example, they observed interactions between muscle cells in heart ventricles; fibroblasts or cells that contribute to the formation of connective tissue; and endothelial cells that line blood vessels. These interactions may play a role in the formation of the heart chamber walls.
“This is a remarkable paper,” Norbert Huebner, professor and group leader at the Max Delbrück Center in Germany, who was not involved in the study, told Live Science in an email. The way the researchers analyzed RNA “serves as a model for understanding organ function at the single-cell level and identifying clinically relevant cellular states and niches in the developing heart,” he said.
The Comprehensive Atlas of the Developing Heart has some very important applications.
“The data are critical for future research into congenital heart disease [heart defects people are born with] and to inform regenerative medicine approaches aimed at replacing lost or dysfunctional myocardium [heart muscle]” Dr. Michela Noseda, a professor and group leader at Imperial College London who was not involved in the study, told Live Science in an email.
Although this atlas is unprecedented in its detail, even better versions are in preparation.
The next step is to create a complete 3D model of the developing human heart, Farah said. Next, the researchers want to track the heart’s development over time to create a “4D atlas of the developing human heart” — essentially a kind of “movie” of heart development that would give scientists a better understanding of this critical process.
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