Researchers at UCL and the Francis Crick Institute have, for the first time, identified the origin of cardiac cells using 3D images of a heart forming in real-time, inside a living mouse embryo.
For the study, published in The EMBO Journal, the teamused a technique called advanced light-sheet microscopy on a specially engineered mouse model. This is a method where a thin sheet of light is used to illuminate and take detailed pictures of tiny samples, creating clear 3D images without causing any damage to living tissue.
By doing this, they were able to track individual cells as they moved and divided over the course of two days — from a critical stage of development known as gastrulation through to the point where the primitive heart begins to take shape. This allowed the researchers to identify the cellular origins of the heart.
Gastrulation is the process by which cells begin to specialise and organise into the body’s primary structures, including the heart. In humans, this occurs during the second week of pregnancy.
The study’s findings could revolutionise how scientists understand and treat congenital heart defects, the researchers say.
Senior author Dr Kenzo Ivanovitch (UCL Great Ormond Street Institute of Child Health and British Heart Foundation Intermediate Research Fellow) said: “This is the first time we’ve been able to watch heart cells this closely, for this long, during mammalian development. We first had to reliably grow the embryos in a dish over long periods, from a few hours to a few days, and what we found was totally unexpected.”
Using fluorescent markers, the team tagged heart muscle cells (called cardiomyocytes) causing them to glow in distinct colours. Combined with light-sheet microscopy, this innovation allowed the researchers to create a detailed time-lapse video.
Snapshots were captured every two minutes over 40 hours, producing images with unprecedented spatial resolution.
The resulting footage showed how cells move, divide, and form the first parts of an embryo, like the heart. Each glowing cardiomyocyte could then be tracked back to earlier cells, allowing scientists to create a family tree of the cells. This helped them see exactly when and where the first cells that only make the heart appeared in the embryo.
At the very earliest stages, embryonic cells were multipotent (capable of becoming various cell types). These included not only heart cells but also others such as endocardial cells, a type of cell that lines the inner surfaces of blood vessels and heart chambers.
However, the researchers found that early during gastrulation (typically within the first four to five hours, after the first cell division), cells contributing solely to the heart emerge rapidly and behave in highly organised ways.
Rather than moving randomly, they follow distinct paths — almost as if they already know where they are going and what role they will play, whether contributing to the ventricles (the heart’s pumping chambers) or the atria (where blood enters the heart from the body and lungs).
Dr Ivanovitch said: “Our findings demonstrate that cardiac fate determination and directional cell movement may be regulated much earlier in the embryo than current models suggest.
“This fundamentally changes our understanding of cardiac development by showing that what appears to be chaotic cell migration is actually governed by hidden patterns that ensure proper heart formation.”
Lead author, PhD candidate Shayma Abukar (UCL Great Ormond Street Institute of Child Health and UCL Institute for Cardiovascular Science) said: “We are now working to understand the signals that coordinate this complex choreography of cell movements during early heart development.
“The heart doesn’t come from a single group of cells, it forms from a coalition of distinct cell groups that appear at different times and places during gastrulation.”
The insights from the study could revolutionise how scientists understand and treat congenital heart defects, which affect nearly one in 100 babies. The findings could also accelerate progress in growing heart tissue in the lab for use in regenerative medicine.
Dr Ivanovitch said: “In the future, we hope this work will help uncover new mechanisms of organ formation. This will inform design principles to precisely program tissue patterns and shapes for tissue engineering.”
The research was supported by the British Heart Foundation.
