Researchers from the Department of Genetics, Microbiology and Statistics and the Institute of Biomedicine of the University of Barcelona (UB), in collaboration with the Center for Genomic Regulation (CRG), have described the genes required in the process of organ and tissue regeneration and the regulating elements of their expression.
The study, which occupied the cover of the prestigious journal Genome Research, combines classical genetic analysis with new techniques for the study of chromatin through high-throughput sequencing technologies, thus providing a new perspective in the field of regenerative medicine.
The research included the participation of Elena Vizcaya Molina (UB) and Cecilia Klein (CRG, UB) first authors of the article led by Montserrat Corominas (UB). It also included the collaboration of researchers Roderic Guigó (CRG), Florenci Serras (UB) and Rakesh K. Mishra (CCMB, Hyderabad, India).
In this article, the authors analyzed the transcriptome of imaginal discs of the wing of Drosophila melanogaster (fruit fly) at different times of regeneration. Through the analysis of massive sequencing of RNA, they identified the genes that are specifically expressed during the process. In addition, they have observed that more than 30% of these genes are located in gene complexes (gene clusters).
Thanks to a comparative analysis with other species (mouse and zebrafish), the authors have also discovered a group of genes involved in regeneration which are found in all of them. “Knowing which genes have in common organisms capable of regeneration can help us understand what is necessary to activate this process in organisms with more restricted regenerative capacities, such as humans,” says Elena Vizcaya Molina.
“This work demonstrates the growing importance of genomics and bioinformatics to understand basic biological processes,” says the postdoctoral researcher at the CRG and UB professor Cecilia Klein. The combination of new sequencing techniques and bioinformatic analysis with experimental work allows us advancing in the understanding the regulation of genes, in this case, of regeneration.
Regulatory elements of regeneration
The authors have also discovered, for the first time, three different types of regulatory elements related to regeneration: those that increase their activity during the process, those that are reused at other stages of development or in other tissues and, finally, a group of elements that are exclusive to regeneration. “These regulatory elements are DNA sequences capable of directing and modulating the expression of genes,” says Vizcaya Molina.
In addition, the researchers observed that these elements can be activated by some of the genes conserved in all the species studied (fly, mouse and zebrafish).
“The ectopic activation of regulatory elements specific to regeneration could be a key tool to stimulate the regenerative capacity of organs that, in principle, are incapable of regeneration“, concludes Montserrat Corominas.
The regeneration has provoked the curiosity of the human being since ancient times, as some legends of Greek mythology demonstrate. However, the regenerative capacity of Drosophila melanogaster was not discovered until the 1940s by one of the fathers of regenerative medicine.
Thomas Morgan observed that the imaginal discs of the fly were capable of regenerating after fragmenting them. Now researchers consider the fly as a good model for the study of regeneration.