Scientists have revealed a new relationship between polyploidy (a phenomenon in which cells contain multiple copies of genetic material) and autophagy (an essential cellular process for recycling damaged or unwanted cellular components that, taken to the extreme, can end up killing the cell itself, in what is known as programmed cell death). Specifically, they have identified a situation in which the level of autophagy increases in cells when the number of their DNA copies increases, even triggering this programmed cell death. This discovery provides insightful new data on the biological processes that shape organisms in their early stages of life and opens the way to a better understanding of developmental diseases and cancer as well.
The finding was made in a study carried out by a team from the Institute for Research in Biomedicine of Barcelona (IRB Barcelona) and the Institute of Molecular Biology of Barcelona (IBMB), dependent on the Higher Council for Scientific Research (CSIC) in Spain.
The team has been led by Dr. Jordi Casanova and Dr. Panagiotis Giannios.
“Polyploidy is a common phenomenon in many species, including humans, although its effects are still largely unknown, and understanding its implications can have a significant impact on medicine,” explains Dr. Casanova, head of the Drosophila Development and Morphogenesis laboratory at IRB Barcelona.
Progenitor cells and polyploidy
Progenitor cells are cells that can give rise to different cell types. In the case of the Drosophila melanogaster fly, the animal model with which this study has been carried out, the progenitor cells are cells of the larva that maintain the capacity to give rise to the adult organism. The progenitor cells do not present polyploidy (they have a single copy of the set of chromosomes) and this allows them to survive metamorphosis and form part of the adult.
“In the case of cancer, it is common for cells to be generated with several copies of DNA (or polyploids) and it could be that this allows them to better resist, for example, chemotherapy treatment. That is why it is important to understand this process”, adds Dr. Giannios, a postdoctoral researcher from the same laboratory.
Total projection of a section of the tracheal dorsal trunk of a third instar Drosophila larva. The nuclei are stained in blue, the cell membrane in red and ref(2)P in yellow. (Image: Beatriz Pino-Jimenez)
Polyploidy in the trachea of the vinegar fly
To study this process, the scientific team worked with the tracheae of the respiratory system of Drosophila melanogaster, which present the same type of cells, some polypoid and others not.
“Working with the trachea of the Drosophila fly has allowed us to compare cells of the same type, some presenting polyploidy and others not, and to see how polyploidy correlates with cell death during metamorphosis,” explains Dr. Beatriz Pino-Jiménez, first author of the paper, who carried out this project as part of her doctoral studies.
The research team is now working to understand whether polyploid cells respond better to stress situations and what are the underlying mechanisms in this response.
The study is titled “Polyploidy-associated autophagy promotes larval tracheal histolysis at Drosophila metamorphosis”. And it has been published in the academic journal Autophagy. (Source: IRB Barcelona)