Writing a molecular atlas of the developing human heart

Heart disease is the leading cause of mortality in the industrialized world, accounting for 40 percent of all deaths in Sweden. Kenneth Chien and his colleagues are trying to understand the molecular basis of heart disease by generating a map of the complex family of heart stem cells that build the human heart.

For adults with advanced forms of heart disease, few treatment options exist, aside from heart transplantation. In children, congenital heart disease is the most common malformation and can be life-threatening, requiring multiple open heart surgeries. Unraveling the cells and molecular pathways that build the human heart will ultimately lead to biologically targeted therapies that address the root causes versus the symptoms of disease. Accordingly, Kenneth Chien and his colleagues will conduct four major projects within the Karolinska CardioVascular Initiative (KCVI).

In the central project, they will capitalize on their recent discovery of the master heart stem cells that build the human heart and provide an atlas of all its cell types and how they talk to each other.

Three new cell types discovered

The Chien lab has previously unveiled three different groups of early heart stem cells that give rise to all diverse cell types in the specific heart compartments (cardiac/pacemaker/vascular muscle, endothelial, and mesenchymal cells). The goal is to generate a high resolution map for how these early cell types expand, migrate, and decide to become specific heart components, integrating genetic insights from congenital heart disease to identify key pathways.

"A detailed cellular map of the developing human heart will uncover the logic for how to regenerate specific heart parts. New technology may allow the regeneration of heart tissue by delivering the molecular cues that guide the rare resident heart stem cells", says Professor Chien.