human cardiogenesis | congenital heart defects self-organization | bridge molecules-cells-tissues training a new generation of scientists
IMBA, Vienna, Austria
Joined July 2017
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I am really happy to share a new preprint from our lab on cardiac repair! To dissect how immune-ECM-cardiomyocyte interactions lead to cardiac repair, we established a modular human cardioid injury platform.
biorxiv.org/content/10.64898…
Is this important? Despite the high incidence, the underlying causes of most cardiac defects remain unknown. We lacked a system to test possible causes in a human context with high throughput in all cardiac compartments. Now we can do it comprehensively and systematically.
Is this useful? We used our high throughput platform to model and dissect how mutations (in ISL1, TBX5, and FOXF1 KO) and environmental factors (thalidomide, retinoids, plastics) cause region-specific defects in the developing human heart, complementing animal models.
ALT The mutation in FOXF1 shows compartment-specific phenotypes in cardioid subtypes with the AVC most affected.
Why is this interesting? The different cardiac progenitors sort, co-develop and functionally connect in multi-chamber cardioids. This allows us to model and study, for the first time, how different regions of the human embryonic heart communicate and coordinate contractions.
How did we do it? By leveraging 2D and 3D differentiation and discovering the signal combinations specifying different cardiac progenitors. This enabled the efficient generation of cardioids with heart region-specific gene expression profiles, morphologies, and functions.
ALT Different cardioid subtypes express specific markers of the five distinct regions of the human embryonic heart: atria, LV (left ventricle), RV (right ventricle), OFT (outflow tract), and AVC (atrioventricular canal).
Two years ago, we reported for the first time on #cardioids. Now, our team, led by two fantastic Ph.D. students, Alison and Clara, developed multi-chamber cardioids representing all the major regions of the human embryonic heart (atria, LV, RV, OFT, AVC) biorxiv.org/content/10.1101/…
Half of our team had a great time at the Weinstein2022 conference last week and we are proud of our Ali for winning a poster award. Many thanks to the organizers for such a great community event - this live interaction was needed so much after the two years of the pandemic.
We also discovered that an inner endocardial lining emerges without the addition of VEGF under similar conditions as left-ventricular specification. It seems to be all encoded at the early stages of mesodermal patterning.
