SCIENTISTS UNVEIL THE SECRETS OF THE HEART USING ZEBRAFISH
What can a small fish tell us about our heart? Surprisingly, quite a lot! The latest molecular studies on zebrafish embryos, published in the journal iScience, shed light on the mechanisms of proper heart development - not just in fish but also in humans.
Researchers from the International Institute of Molecular and Cell Biology in Warsaw (IIMCB), in collaboration with the Nencki Institute and Jagiellonian University, profiled the transcriptome (the pool of RNA present in a cell) of over 50,000 individual cells that make up the heart of the zebrafish. Utilizing one of the most advanced RNA sequencing technologies for single cells (scRNA-seq), they determined which genes are active in specific cells at various stages of the animal's embryonic development. One of the most significant findings was the discovery of diverse populations of cells that form the heart muscle, including a rare group of pacemaker cells that regulate the heart's rhythm and function
Photo: Creators of the atlas of single cells of the developing heart of the zebrafish, scientists from the IIMCB's Laboratory of Zebrafish Developmental Genomics: (from right) study leader Dr. Cecilia Winata, main author Dr. Karim Abu Nahia, supported by Dr. Agata Sulej (photo: FNP)
"Our detailed analyses of the specialized group of pacemaker cells revealed at least two new genes involved in maintaining the heart's rhythm: atp1b3b and colec10. This discovery opens the door to identifying new biomarkers (indicators) and molecular factors (substances) involved in both heart development and the emergence of heart diseases. These results pave the way for in-depth heart research and could potentially lead to innovative diagnostic and therapeutic methods in cardiology," says Dr. Cecilia Lanny Winata from the Laboratory of Zebrafish Developmental Genomics at the IIMCB.
What Does the Fish Say
The zebrafish (Danio rerio) is a tropical freshwater fish native to South Asia, popular in aquarium breeding. Though small and inconspicuous, it plays an important role in science. Thanks to its high compatibility with human genetic and molecular mechanisms, the rapid development of optically transparent embryos, and the ease of genetic modifications, it serves as a model organism for biological research.
"Decades of scientific work have enabled the identification of fundamental molecular mechanisms common to both zebrafish and mammals," explains Dr. Winata.
The study published in iScience revealed that both the heart muscle and the endocardium (the inner layer of the heart wall) of the zebrafish contain cell types with different molecular profiles. This suggests early cell specialization in terms of their functions. This diversity appears to be conserved across different animal species, as similar results have been noted in mammalian studies. As the researcher points out, before technology was available for biological studies at the single-cell level, the diversity of cells forming the heart was not well understood.
" We were struck by the finding that the fish heart is composed of much more diverse cell types than previously thought. Our analyses identified at least 18 distinct cell populations encompassing the major developmental lineages of the heart and their numerous sublineages. Such discoveries open up possibilities for a more detailed and precise study of the heart and its functions," concludes Dr. Cecilia Winata.
Molecular Atlas of the Heart
Dr. Winata's team's research resulted in the creation of a comprehensive atlas of cell lineages of the developing zebrafish heart. This open and online data set consists of over 50,000 individual cells involved in the organ's formation during the embryonic stage. As the researcher notes, the publicly available atlas enables in-depth analysis of specific heart cell types, serving as a source of knowledge for the global scientific community.
"Our findings may offer new perspectives for clinicians working with congenital heart defects, potentially aiding the design of innovative diagnostic and interventional strategies. Additionally, they pave the way for more detailed studies of heart function, contributing to advancements in precision medicine," emphasizes Dr. Cecilia Lanny Winata from the International Institute of Molecular and Cell Biology in Warsaw.
An atlas of the cell lineages of the developing zebrafish heart is available at: http://zfcardioscape.iimcb.gov.pl/
An article in iScience titled "scRNA-seq reveals the diversity of the developing cardiac cell lineage and molecular players in heart rhythm regulation": https://tinyurl.com/53kpfpsw