IRB Barcelona opens new lab devoted to cellular lineage and identity.
The study of cell lineages seeks to clarify how different types of cells are generated and the important implications of this process for the development of an organism, as well as for cancer.
The cells of a living organism share the same DNA, the same instruction book, and yet each cell develops a unique identity. Alejo Rodríguez-Fraticelli (Buenos Aires, Argentina, 1985), a researcher specialising in the study of cell lineages, joins IRB Barcelona to lead the new "Quantitative Stem Cell Dynamics" laboratory.
Stem cells are characterised by their pluripotency, meaning the ability to give rise to different cell types. Indeed, this capacity is essential during development, when a single cell brings about an entire organism, and it is pivotal in cancer because it is the cancer stem cells that maintain that potential to regenerate a tumour after it has been removed, or to colonise other organs, in a process known as metastasis. With the aim to provide new therapeutic perspectives, cell lineage tracing allows the identities and fates of thousands of cells to be linked simultaneously, and also the prediction of those cells most likely to metastasize.
"Our field of study is devoted to cell lineages and the regulation of cell identity, but above all, we will be a technology-driven laboratory, constantly focused on developing the next generation of genetic tools that allow us to answer more complex questions," says Rodríguez-Fraticelli.
Cell identity and blood cells as a model
Since the beginning of his career, Rodriguez-Fraticelli has worked with two highly regenerative cell types, namely epithelial cells (skin, kidney and intestine) and hematopoietic (blood) cells, which include immune system cells. In recent years, his research has focused on the latter.
"I saw that working with blood cells had many advantages for what I wanted to study, which was regeneration and cancer biology," Rodriguez-Fraticelli explains, "there is a lot of prior knowledge, many tools and, ultimately, the field was ready for such approaches. I think it was a good move to start working with these cells." "We started to get results right away and in the first few months I realised that we were on the verge of a breakthrough," he adds.
His discovery that, against what was previously believed, multiple hierarchies coexist within the bone marrow and coordinate the cell origin of hematopoietic cells was published in Nature in June 2020. One of his lab's lines of research will focus on determining whether this multiplicity of hierarchies confers hematopoietic cells adaptability and plasticity to deal with damage such as an infection or loss of a lot of blood.
Another line of study pursued by the lab will address a recurring concept in cancer, the cancer-initiating cell, specifically they seek to unravel the state that a cell needs to be in for a mutation to trigger a tumour. The lab will also examine cell lineages in the context of ageing.
"All our adult tissues are made up of a defined set of clones, that is, cell families. Like real families, cell families also have 'customs' and 'inheritances' that are passed on to descendants. One of these inheritances passed from generation to generation is which DNA instructions have to be read and which don’t, this is what we call 'epigenetics'. This is precisely where we think the keys lie as to why some cells mutate and give rise to cancer and others don't. Or why some cells progress toward metastasis and others don't," says Rodriguez-Fraticelli.
The career of Alejo Rodríguez-Fraticelli
Rodríguez-Fraticelli studied Biology and then Biochemistry at the Autonomous University of Madrid and, from the very outset, he knew that he wanted to pursue a career in research. His first contact with the laboratory, on the recommendation of his immunology professor, scientist and science disseminator Jose Antonio Lopez Guerrero, was at the Severo Ochoa Center for Molecular Biology (CBMSO), in Miguel Angel Alonso’s group. There, he learned the bases of molecular biology and microscopy by studying epithelial cells and lymphocytes. He did his doctoral thesis on epithelial biology, using 3D cell cultures—organoids—under the supervision of Fernando Martín Belmonte, also at the CBMSO.
In 2015, Alejo Rodríguez-Fraticelli took up a postdoctoral position in Fernando Camargo's laboratory at Harvard University and Boston Children's Hospital, where he specialised in single-cell technologies and the tracing of cell lineages in both development and cancer to understand the bases of cellular heterogeneity. "When I was interviewed by Fernando, it was as if someone opened the door to a world of biology that I didn't know about," says Rodríguez-Fraticelli, "he was clearly interested in the development and size of organs, but his mind went far beyond what I had ever thought and I knew straight away that I had to join that lab."
He has published more than 20 scientific articles, among these two in Science and Nature this year and in which he appears as first author.
IRB Barcelona's commitment to young talent
In addition to Alejo Rodríguez-Fraticelli, Cristina Mayor-Ruiz has also recently joined IRB Barcelona. Both are talented young researchers who are starting a new stage of their careers as group leaders. The onboarding of these two researchers is part of the centre's commitment to recruiting young talent with exceptional potential and offering them leadership opportunities.
"What appeals to me most about IRB Barcelona is the number of groups with which I think I will be able to find synergies and collaborate," says Rodriguez-Fraticelli, "I look forward to learning from the experience of other groups and to being able to test my tools in other organs and tissues." "Also, IRB Barcelona is committed to taking research results closer to clinical practice while also allowing researchers the freedom to explore challenging questions, which I think is crucial," he adds.
