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In various blood cells such as red blood cells and lymphocytes , phagocytocytes, including macrophage and neutrophils, are considered to be the oldest blood cells in evolution, because phagocytocytes can be found in any animal, including the very simple morphological multicellular organism , such as sponge . It is speculated that the evolved initial blood cells appear in the form of phagocytic cells in the common ancestor of animals, and various non-phagocytic lineages evolved from the original phagocytic cells during evolution. Based on the fact that each lineage evolved from phagocytic cells of the ancestors, the retention of the potential of phagocytic cells in these lineage progenitors is a relic of the phylogenetic process. It has been found that mice, sharks, bone fish and frogs' platelet , red blood cells and B cells have phagocytic potential.
However, this speculation is not based on genetic evidence and it is still possible to think that phagocytocytes of different species have different origins. In addition, how the initial blood cells evolved remains to be clarified: did ancient animals develop de novo programs for phagocytosis alone, or did they inherit a key program from their ancestors’ single-cell organisms?
Recently, the Hiroshi Kawamoto team published the journal BloodTracing the evolutionary history of blood cells to the unicellular ancestor of animals article, compares the gene expression profiles of phagocytic and non-phagocytic cells of various animals and single-cell organisms, and finds that their phagocytic cells are similar on transcription , sharing CEBPa and its homologue-driven phagocytic programs. In mice, CEBPa was inhibited by Polycomb to maintain the function of non-phagocytic lineage cells. These findings suggest that single-cell biological programs driven by CEBPa are also seamlessly inherited throughout the evolutionary process in phagocytic cells of various animal species.
research team first compared the gene expression profiles of mice, cyst animal , sponge and a single-cell organism (Capsaspora) , and the gene expression profiles of cells of different lineages or stages of four species. Among invertebrates, cystic animals belong to chords and are close to vertebrates, while sponges are the oldest animals and the farthest from vertebrates. It was found that macrophages were more similar to Capsaspora than non-phagocytic and neutrophils in blood cells. Since hepatocytes, fibroblasts and adipocytes also have phagocytic potential, these three cells are classified as phagocytic cells with macrophages, and it was found that phagocytic cells are highly similar to Capsasapora. After examining the highly expressed genes shared by various cell lineages in mice with Capsaspora, it was found that macrophages shared more of lysosome-related genes with Capsaspora.
Further, the authors sought to reveal which transcription factors (TF) play a key role in Capsaspora and mouse phagocytocytes. It was found that 62 TFs were conserved in 4 species, and CEBPα was the only highly expressed TF in Capsaspora and mouse macrophages. CEBPα is expressed at the filamentous or cystic stage of Capsaspora than the aggregation stage, while PLA2G15 (a lysosomal protein that plays a role in host defense and human phagocytosis) is also highly expressed at the filamentous and cystic stages, indicating that the CEBPα-driven phagocytosis program expressed by PLA2G15 is conserved in single cells and vertebrates. In addition, CEBPα homologs are also highly expressed in cysts and sponge phagocytocytes.
In mouse blood cells, CEBPα acts as the main regulator of phagocytic or myeloid cells, i.e., it has the potential to convert non-phagocytic lineage progenitor cells into myeloid cells, which means that CEBPα must be strictly inhibited to maintain non-phagocytic characteristics.The authors finally found that Polycomb (polycomb complex, one of the main epigenetic inhibitors) usually inhibits CEBPα in various non-phagocytic lineage cells, exerting the role of inhibiting phagocytic procedures. Knocking out Ring1a/b in Polycomb can transform non-phagocytic lineage cells into phagocytic cells, but overexpression does not convert phagocytic cells into non-phagocytic lineage cells, indicating that Polycomb only plays a role in maintaining non-phagocytic lineage.
In summary, this study provides an in-depth understanding of the origin of blood cells in the animal kingdom. where primary phagocytocytes in animal ancestors are generated by activating CEBPα-driven phagocytosis programs inherited from single-cell organisms, and elucidating Polycomb-mediated epigenetic inhibition of CEBPα is a molecular mechanism that maintains the function of non-phagocytosis lineage cells in vertebrate hematopoiesis.
Original link:
https://doi.org/10.1182/blood.2022016286
https://doi.org/10.1182/blood.2022016286
Platformer: Eleven
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