The most detailed map to date of a developing human heart has revealed that cardiac cells organize into communities and interact with their environment. This context in turn determines the function of each cell, and lays the foundations on which the structures of the adult heart later develop. The atlas, published this Wednesday in the journal Nature, will improve the understanding and treatment of heart diseases.
Scientists at the University of California San Diego (UCSD) have analyzed the hearts of eleven fetuses between 9 and 16 weeks to create the map. They have done so by combining two extraordinarily precise techniques: one, called RNA sequencing, which has allowed them to identify the different types of cells present in the organs being formed; and another, nicknamed MERFISH, which has located each one in space.
This double analysis has revealed that up to 75 different types of cells are involved in the development of the heart, which are not distributed uniformly, but rather are organized into 13 groups (or cellular communities). These groups of cells are the precursors of the different tissues that make up the adult heart.
“Knowing only the cell types within an organ is not enough to understand how it works,” explains Elie Farah, a postdoctoral researcher at UCSD and one of the authors of the article, in statements to La Vanguardia. “The organization of cells is a critical part of the assembly process to create a fully functional organ,” because “the whole is more than the sum of the parts,” he concludes.
That is why its map represents a leap forward in the knowledge of how the human heart is formed. It not only lists the cells involved with a level of detail greater than current knowledge, but also details their organization. The combination of both factors sheds light on why the complex structures that make up the organ have a certain shape and function.
The bulk of the heart is made up of four large chambers: the atria (the upper two, which receive blood from the blood vessels) and the ventricles (the lower ones, responsible for pumping it to the rest of the body). It is not surprising, then, that most of the cellular communities that scientists have identified are involved in their formation. The rest make up other smaller (but equally important) regions, such as the tricuspid and mitral valves, which regulate the passage of blood from one chamber to another.
The map points to the ventricles as the most complex regions in terms of cellular organization. There, the different groups of cells are distributed in layers, which give shape to the cavity wall, especially thick in the left ventricle. This complexity caught the attention of researchers, who decided to focus their efforts here to understand how these groups of cells evolve to form the definitive cardiac structures.
To do this, they analyzed mouse hearts and performed in vitro tests with stem cells of human origin. Both experiments revealed the same thing. The cells that make up the left ventricular wall communicate with each other, sending chemical signals that regulate their development and, therefore, that of the cardiac tissue.
“Groups of cell types mark and influence each other's specialization, which, in turn, allows them to cooperate and achieve the specific function of each structure,” explains Farah. That is to say, ultimately, the role that each cell plays in the adult heart depends on where it is located and how its companions act. This ends up being key in the final development of the organ.
So much so that any problem in the formation of these structures can end up leading to cardiac pathologies, both congenital - the most common birth defects - and acquired in adulthood. UCSD scientists hope that their cardiac map will contribute to understanding, in the future, how these diseases originate.
“It could also be used to develop biologically relevant cardiac organoids and tissues that can be used as a platform to identify drugs and regenerative cardiac therapies,” explains Farah. These may be some of the treasures that the map hides, and that future research should reveal.
