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The earliest known progenitor of the outermost layer of the heart has been characterised for the first time and linked to the development of other critical cell types in the developing heart in a new paper from the Srinivas group led by BHF Immediate Fellow Dr Richard Tyser.

Frontal view of a developing mouse heart used in the study

The heart is the first organ to form during development and is critical for the survival of the embryo. The forming heart is very small, less than half a millimetre in width, and so far the precise molecular identity of the various cell types that make up the heart during these early stages have been poorly defined. However, recent years have seen rapid development in techniques which allow an unbiased assessment of molecular identity at the single cell level. Alongside this, advances in imaging technologies have now allowed researchers to visualise heart formation at high resolution and in real time.

In new research from the Srinivas Group led by Dr Richard Tyser and Dr Ximena Ibarra-Soria, the team combined these cutting-edge technologies to profile the molecular identity and precise locations of cells involved in the formation of the mouse embryonic heart. This allowed them to identify the earliest known progenitor of the epicardium, the outermost layer of the heart and an important source of signals and cells during cardiac development and injury.

Dr Tyser said: “The epicardium is known to have a role in both development and disease, especially following a heart attack when it can generate cells required for repair such as fibroblasts, vascular smooth muscle and cardiomyocytes. This study could be therapeutically applicable at two levels: first, understanding the origins of congenital heart defects and second, providing insight into regenerative strategies to treat heart disease.”

The epicardium forms from a tissue called the proepicardium and the origin of this tissue has been unclear to the research community for some time. Additionally, while the epicardium has been profiled in the past, this has only been done during later stages of embryonic development. In a new paper published in Science, Dr Tyser and Dr Ibarra-Soria’s research marks the first time the cells that give rise to the epicardium have been profiled and anatomically localised. In doing so, the team not only identify a new group of cells that give rise to the proepicardium, thus revealing its origin, but they also show that this group of cells can also directly give rise to a second type of heart cell: cardiomyocytes, which are responsible for enabling the heart to contract and thus pump blood around the body.

According to Dr Tyser: “This study has opened up a number of different lines of research. Having characterised the molecular identity of the different progenitor cell types in the forming heart we will now investigate how these progenitors initially form, their lineage relationship and the role of specific genes, identified in this study, during heart development and disease.”

The research was produced in collaboration with John Marioni (University of Cambridge) and Philipp Keller (HHMI Janelia Research Campus).

The full paper “Characterization of a common progenitor pool of the epicardium and myocardium” is available to read in Science.

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