Lymphoid commitment during development

Project: Research

Description

How do hematopoietic stem cells (HSC) differentiate into mature blood cells? Knowledge of how lineage commitment occurs during normal haematopoiesis is important if we are to understand underlying events that lead to leukaemia. The route to produce mature blood cells can be thought of as a hierarchical tree, with rare HSCs at the top, cells that give rise to all other cells and progenitors of the blood system and that can also self renew. Lineage commitment has been extensively studied in the adult mouse system, but less is known about the process during development. Understanding the process of lineage commitment during development and how it differs from the adult system is important since several mutations leading to childhood acute lymphoblastic leukaemia (ALL) are known to arise already in utero.

We have recently identified the first lymphoid commitment step in the early mouse embryo and found and characterized a progenitor restricted to the immune system. The progenitor expressed the recombination activating gene 1 (Rag1) and was developmentally the earliest immune-restricted cell emerging before definitive HSCs. By using Rag1-fate mapping we could elucidate that the embryonic immune restricted progenitor in contrast to adult bone marrow contributed to myelopoiesis in vivo (Böiers et al, Cell Stem Cell 2013). These data clearly show differences between foetal and adult lymphopoiesis, differences that needs to be further explored. Corresponding differences might also exist in the human system and we have ongoing investigations to explore this in normal human development.
StatusNot started

Participants