1013 – VARIOUS IMMUNE CELL DEVELOPMENT FROM EMBRYOS TO ADULTS

Recently, many pieces of evidence indicate that blood cell development in the embryo is more complicated than we previously thought. Old textbooks state that the first blood cells arise in the extra-embryonic yolk sac described as transient primitive hematopoiesis, followed by definitive hematopoietic stem/progenitor emergence in the aorta-gonad mesonephros (AGM) region. These HSPCs migrate to the fetal liver and maintain fetal hematopoiesis. HSCs migrate to the bone marrow before birth and establish adult-type hematopoiesis for life. However, we and others recently reported that fetal liver hematopoiesis is supported by HSC-independent hematopoietic progenitors and the fetal-derived (HSC-independent) immune cells persist into adult life much longer than we expected. Using lineage tracing mouse models, we precisely examined the percentage of HSC-derived cells in each hematopoietic lineage and found that not 100% of cells are derived from HSCs. Instead, hematopoietic cells derived from endothelial cells in the early embryo contribute to many immune cell populations. These results were also confirmed by transplantation assays. We also identified the earliest innate lymphoid progenitors in the fetal liver. These cells arise independently of HSCs and differentiate into peritoneal B-1 cells, intestinal IgA+ cells, some T cells, and mast cells. We also examined detailed BCR of fetal-derived and HSC-derived B-1 cells.

Our data display a new paradigm in which immune cells are a mixture of cells from different origins and could function differently.