Periodic Reporting for period 3 - TransReg (Transgenerational epigenetic inheritance of cardiac regenerative capacity in the zebrafish)
Période du rapport: 2022-08-01 au 2024-01-31
While myocardial infarction leads to adverse ventricular remodeling ultimately causing heart failure in humans, some animals, including zebrafish can regenerate the injured heart. For regeneration to occur, cardiac muscle cells in the zebrafish can repopulate the lost heart muscle. For this they can enter cell division and afterwards re-acquire their contractile functions. We want to understand if all cardiomyocytes have the same capacity to contribute to heart regeneration. Furthermore, we wonder if a memory of an injury is retained in the tissue or whole organism that could influence future injuries. We are particularly interested in understanding if a cardiac injury memory persists from one generation to the next and, if that is the case, it this could influence regenerative capacity of offspring.
Unravelling the mechanisms that allow natural heart regeneration in some species could inspire the development of regenerative therapies for humans. Also, knowing if and how experiences affecting health can be transmitted to subsequent generations is of relevance for the understanding of disease.
Unravelling the mechanisms that allow natural heart regeneration in some species could inspire the development of regenerative therapies for humans. Also, knowing if and how experiences affecting health can be transmitted to subsequent generations is of relevance for the understanding of disease.
In this period we refined the methods for reproducible experimental conditions that are essential for correctly interpreting our results.
On the one hand we updated the protocol for cardiac regeneration assessment. The updated protocol for cardiac cryoinjury was published: Marques IJ, Sanz-Morejón A, Mercader N. Ventricular Cryoinjury as a Model to Study Heart Regeneration in Zebrafish. Methods Mol Biol. 2021;2158:51-62. doi: 10.1007/978-1-0716-0668-1_5.
On the other hand we analyzed the content of metals and metalloids in the fish tank water, as high concentrations of certain compounds can affect welfare and therefore, eventually even sublethal concentrations might affects animals under an experimental procedure. We reasoned that it is therefore important to be aware of which is the expected concentration of metals and metalloids to be found in a recirculating water system as the one used in zebrafish facilities.
The results from that study were published: Langa X, Neuhaus P, Lains D, Stewart TJ, Borel N, Certal AC, Monteiro JF, Aleström P, Diaz E, Piragyte I, Bräutigam L, Vázquez R, Hlushchuk R, Gfeller L, Mestrot A, Bigalke M, Varga ZM, Mercader N. A Systematic Analysis of Metal and Metalloid Concentrations in Eight Zebrafish Recirculating Water Systems. Zebrafish. 2021 Jul 5. doi: 10.1089/zeb.2020.1970. Epub ahead of print. PMID: 34227897.
We reviewed the recent findings on the mechanisms of zebrafish heart regeneration: Sanz-Morejón A, Mercader N. Recent insights into zebrafish cardiac regeneration. Curr Opin Genet Dev. 2020 Oct;64:37-43. doi: 10.1016/j.gde.2020.05.020. Epub 2020 Jun 26. PMID: 32599303.
On the one hand we updated the protocol for cardiac regeneration assessment. The updated protocol for cardiac cryoinjury was published: Marques IJ, Sanz-Morejón A, Mercader N. Ventricular Cryoinjury as a Model to Study Heart Regeneration in Zebrafish. Methods Mol Biol. 2021;2158:51-62. doi: 10.1007/978-1-0716-0668-1_5.
On the other hand we analyzed the content of metals and metalloids in the fish tank water, as high concentrations of certain compounds can affect welfare and therefore, eventually even sublethal concentrations might affects animals under an experimental procedure. We reasoned that it is therefore important to be aware of which is the expected concentration of metals and metalloids to be found in a recirculating water system as the one used in zebrafish facilities.
The results from that study were published: Langa X, Neuhaus P, Lains D, Stewart TJ, Borel N, Certal AC, Monteiro JF, Aleström P, Diaz E, Piragyte I, Bräutigam L, Vázquez R, Hlushchuk R, Gfeller L, Mestrot A, Bigalke M, Varga ZM, Mercader N. A Systematic Analysis of Metal and Metalloid Concentrations in Eight Zebrafish Recirculating Water Systems. Zebrafish. 2021 Jul 5. doi: 10.1089/zeb.2020.1970. Epub ahead of print. PMID: 34227897.
We reviewed the recent findings on the mechanisms of zebrafish heart regeneration: Sanz-Morejón A, Mercader N. Recent insights into zebrafish cardiac regeneration. Curr Opin Genet Dev. 2020 Oct;64:37-43. doi: 10.1016/j.gde.2020.05.020. Epub 2020 Jun 26. PMID: 32599303.
With our studies we aim to understand whether a cardiac injury in a parental generation can influence the regenerative capacity of subsequent generations.