Mouse heart map clues researchers in on human heart maturation

The heart is a complex organ. And it’s not simple to create. But a recent study on the development of mouse hearts has provided some insight into the genetic programing needed to create a human heart and what mutations can lead to congenital heart defects.

Researchers at Harvard University used RNA sequencing techniques to create an atlas of a mouse heart.

Jonathan Seidman, the Henrietta B. and Fredrick H. Bugher Foundation Professor of Genetics at Harvard Medical School, and colleagues sampled heart cells from seven different stages of embryonic development in mice and sorted them into three known categories: myocardial cells, endothelial cells and fibroblasts. They then observed how each group’s genetic activity changed over time.

"The study provides both a temporal and spatial atlas that plots the development of the different cell populations in each of the four chambers,” Seidman said. "The converse is also true: By looking at a cell's RNA expression, we can gather clues to its origins."

The results helped to clarify which cell types are present in various parts of the heart during each time period. A previously unknown cell type was also discovered. Researchers were also able to describe errors in specific cell types in mice with a genetic mutation that causes congenital heart defects in humans.

While mouse hearts and human hearts are not identical, they are similar in many ways—both have a four-chambered structure, electrical signals that direct muscle contraction and relaxation and similar molecules that are involved in muscle function.

"The hope is that now we're beginning to understand at a single-cell level how perturbations in genes and cells lead to changes in cardiac structure and clarify what the important steps are for how the heart is built," Seidman said.

Going forward, the team plans to investigate how the particular genetic that lead to congenital heart disease can cause the changes in heart development pediatric cardiologists have been tracking for years.