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Determining the relationships between haematopoietic lineages using genetic barcoding

Final Activity Report Summary - GENETIC BARCODING (Determining the relationships between haematopoietic lineages using genetic barcoding)

The way in which white blood cells grow in the body, known as haematopoiesis, is a very important issue to understand so that we may better target diseases such as leukemia and lymphoma, or boost the immune system of patients after an infectious disease or chemotherapy. The current concepts state that a haematopoietic stem cell is like a seed that grows into a tree, able to generate all different branches and leaves of the white blood cell family. Most relevant studies focused on testing a large number of these cells, e.g. thousands, in mouse models. However, in order to truly understand how this process occurs, we must understand how each of those thousand cells contributes.

A new technology, termed ‘cellular barcoding’ was used to study this process by tagging up to 5 000 cells with a unique identifier barcode. In this way, I tracked how hundreds of single cells made the different cell types. Our preliminary data suggested that, unlike a hematopoietic stem cell (HSC) that produced many different white blood cell types, there were many different stem cell types that could sometimes make only one or two white blood cell types rather than all of them. This had important implications in how we understood development in general, and how this might be applied to therapy.