Article content

Humans are born with one heart, which contains nearly all the muscle cells an individual will have throughout their lifetime, says Ellie Farrar, Ph.D., a postdoctoral fellow at the University of California, San Diego School of Medicine. It says that there is. . He added that heart muscle cells primarily grow after birth through a process called hypertrophy. “But they don’t regenerate into adulthood. They don’t grow back,” he added.

But Farrar said that heart cells do form communities and have surprisingly sophisticated forms of biochemical communication. A thorough understanding of the cardiac cell community is important for cardiac finite cell number studies, as cell miscommunication can lead to congenital cardiac birth defects and several types of heart disease in adults. .

Farrar is the lead author of a new study that was recently published. Nature This emphasizes the importance of correct cell phone communication. If the structure of the heart muscle does not form properly, it can lead to congenital heart disease, the most common birth defect. Some adult heart diseases may also develop. Farrar said the left ventricle is a known problem area: “The left ventricle pumps blood throughout the body, so if the left ventricle stops working, that’s heart failure.”

A common left ventricular disease is hypertrophic cardiomyopathy, in which the walls of the left ventricle become stiff and the heart becomes less efficient at pumping blood. Another condition in adults is valvular heart disease, where the heart valves don’t open and close properly. Many of these problems result from impaired cellular interactions between the cellular communities and subcommunities that make the heart function.

“You can actually think of the heart as being like people’s actual neighborhoods,” Farrar explained. “When you put together a group of neighborhoods, you get a city.”

The neighborhoods that make up the cardiac community are organized into specific cardiac structures that are important for cardiac function. These include her four heart chambers: the left and right atria, and the left and right ventricles. The right atrium receives hypoxic blood and pumps it into the right ventricle, which pumps it to the lungs. The left atrium receives oxygen-rich blood from the lungs and pumps blood to the left ventricle, which pumps blood to the rest of the body.

Farrar said each of these chambers requires very specialized cells that produce the proteins needed to perform specific functions. They used his two techniques to analyze the groups of cells that make up specific chambers of the heart muscle. One is single-cell RNA-sequencing, which allows profiling of every single cell within the heart. The second is MERFISH, a single molecule imaging process.

“We integrated these two techniques to define communities and investigate cell-cell interactions within them,” he said, gaining insight into the expression and spatial location of 238 genes. Ta.

They paid particular attention to the vital left ventricle, finding what Farrar described as “layered tissue.” As the team explored the layers, they discovered that each layer was its own separate community. They began investigating cell-cell interactions and discovered that cells within a layer communicate with each other through signaling pathways.

Their research suggests that one such pathway, the plexin semaphorin, may be involved in a process known as ventricular compression, which smooths and stiffens ventricular muscles during prenatal development. We have proof.
“We found a single signaling pathway that may be involved, and defects in that pathway can cause non-compression, potentially affecting many heart failure patients. “It could be some type of cardiomyopathy,” he said. They also discovered a previously uncharacterized, highly specialized cell type that may be important for heart valve development.

Research from the University of California, San Diego provides a more complete understanding of cellular development in the heart and provides insight into the development of a variety of new cardiac diagnostic strategies and treatments. For example, Professor Farrar said that by culturing the right cells in vitro, it could be possible to create a “model of the developing heart in a dish” that could be used for drug screening or regenerative therapy.

All co-authors are from the University of California, San Diego: Quan Zhu and Neil C. Chi (co-corresponding authors), Robert K. Hu, Colin Kern, Qingquan Zhang, Ting-Yu Lu, Qixuan Ma, Shaina Tran, Bo Zhang, and Daniel. Carlin, Alexander Monell, Andrew P. Blair, Jill Wang, Jacqueline Eschbach, Bing Li, Oijing Destici, Bing Ren, Sylvia M. Evans, and Xiaochen Chen.

This research was funded in part by the California Institute for Regenerative Medicine (GC1R-06673-B) and by a grant from the NIH to BR, SME, Q. Zhu and NCC, Chan Zuckerberg Initiative (2023). Partially supported. -321230) to BR, Q. Zhu and NCC, NSF (2135720) to SC

Competing Interests: Bing Ren is a shareholder and consultant at Arima Genomics and co-founder of Epigenome Technologies. All other authors declare no conflicts of interest.