7億年にわたる血液細胞の家系図―T細胞の祖先はマスト細胞だった―

This study provides a transcriptome-based model for the evolutionary history of animal blood cells, from emergence to divergence. The initial blood cells emerged in early animals inheriting unicellular ancestors’ features, followed by the evolution of mast cells in bilaterian ancestors to fight against parasites. Thereafter, in deuterostome/vertebrate ancestors, T/NK cells and erythrocytes/thrombocytes arose from the ancestral mast cells, while B cells evolved from the ancestral macrophages. Along with diversification of blood cell lineages, prototypic thymus formed at the gill edges in chordate ancestors. We finally found a vestige of the evolutionary history in murine hematopoiesis by detecting widely retained macrophage and mast cell potential. These findings shed light on a reciprocal relationship between the evolutionary history and current development pathways.

Blood cells are common and unique to animals, enabling them to address critical challenges of defense and transport. Thus, their evolution represents a defining innovation in metazoan multicellular life. However, their evolutionary trajectory about how blood cells emerged and diversified throughout animal history remains unclear. Here, we present a combination of bioinformatics and functional data that demonstrate that the metazoan blood cell program most likely originated through the repurposing of an ancestral premetazoan toolkit governed by Fos. This primordial program established the macrophage-like initial blood cells at the metazoan root. Then, the first lineage bifurcation at the origin of Bilateria drove the emergence of a specialized mast/killer lineage, characterized by acquisition of granular proteases for antiparasitic defense. Subsequent deuterostome/vertebrate innovations branched T/NK and erythrocyte/thrombocyte lineages from mast cells while B cells derived from macrophages. Our data also show that a prototypic thymus formed at the gill edges of a chordate ancestor. In line with the evolutionary history, the modern hematopoietic pathway shows a vestige of the phylogeny; differentiation potentials of phylogenetically old cell lineages expressing Fos such as macrophages and mast cells are widely retained, and ancient HSCs with limited lineage potentials have been inherited as origo-lineage progenitors. Our framework provides the history of blood cells showing an adaptive innovation built upon ancient unicellular foundations.