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The mechanisms of proper heart development, including the natural pacemaker mechanism, have been described by scientists thanks to the analysis of laboratory zebrafish embryos.
Researchers from the International Institute of Molecular and Cell Biology in Warsaw (IIMCB), in collaboration with the Nencki Institute and the Jagiellonian University, profiled and described in the journal iScience 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), the researchers have 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.
'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 IIMCB.
WHAT WILL THE FISH TELL?
The zebrafish (Danio rerio) is a tropical freshwater fish native to South Asia, popular in aquarium breeding. Small and inconspicuous, it still plays an important role in science, as it serves as a model organism for biological research.
Scientists use this species because it has many similarities to humans in terms of genetic and molecular mechanisms. Moreover, these fish can be easily subjected to genetic modifications and their embryos develop quickly and are transparent, which makes it easy observe their functioning.
'Decades of scientific work have enabled the identification of fundamental molecular mechanisms common to both zebrafish and mammals', says Dr. Winata.
The study reveals 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. The researcher points out that before technology was available for biological studies at the single-cell level, the diversity of cells forming the heart was not well understood.
'Such discoveries open up possibilities for a more detailed and precise study of the heart and its functions. 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', says Dr. Winata.
MOLECULAR ATLAS OF THE HEART
The 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.
According to Dr. Winata, 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', says Dr. Winata.
The atlas of the cell lineages of the zebrafish heart is available here. (PAP)
PAP - Science in Poland
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