Animals have expanded the evolutionary legacy of unicellular ancestors in blood cells

• 成果类型: Article
• 署名作者: Nagahata, Yosuke; Nishimura, Yuji; Kaitani, Ryota; Leong, Jason Cheok Kuan; Oda-Ishii, Izumi; Kohtsuka, Hisanori; Abe, Shinya; Ishida, Tasuku; Carmona-Rivas, Marina; Najle, Sebastian R.; Casacuberta, Elena; Ikuta, Koichi; Miura, Toru; Ogasawara, Michio; Irie, Naoki; Satou, Yutaka; Ruiz-Trillo, Inaki; Kawamoto, Hiroshi
• 署名单位: Kyoto University; Consejo Superior de Investigaciones Cientificas (CSIC); Pompeu Fabra University; CSIC-UPF - Institut de Biologia Evolutiva (IBE); Japan Society for the Promotion of Science; Graduate University for Advanced Studies - Japan; Kyoto University; University of Tokyo; Kyoto University; Institute of Science Tokyo; Universitat Internacional de Catalunya (UIC); Chiba University; ICREA
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2528110123
• 发表日期: 2026-06-09
• 页码: e2528110123
• 关键词: blood cell; EVOLUTION; unicellular organism; mast cell; thymus; VARIABLE LYMPHOCYTE RECEPTORS; GENE-EXPRESSION PROFILES; transcription factors; CIONA-INTESTINALIS; LINEAGE COMMITMENT; myeloid progenitor; CYTOTOXIC ACTIVITY; mast-cells; granzyme-b; t-cells

摘要

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.