Tracing the evolutionary history of blood cells to the unicellular ancestor of animals

Abstract

Blood cells are thought to have emerged as phagocytes in the common ancestor of animals followed by the appearance of novel blood cell lineages such as thrombocytes, erythrocytes, and lymphocytes, during evolution. However, this speculation is not based on genetic evidence and it is still possible to argue that phagocytes in different species have different origins. It also remains to be clarified how the initial blood cells evolved; whether ancient animals have solely developed de novo programs for phagocytes or they have inherited a key program from ancestral unicellular organisms. Here, we traced the evolutionary history of blood cells, and cross-species comparison of gene expression profiles revealed that phagocytes in various animal species and Capsaspora (C.) owczarzaki, a unicellular organism, are transcriptionally similar to each other. We also found that both phagocytes and C. owczarzaki share a common phagocytic program, and that CEBPα is the sole transcription factor highly expressed in both phagocytes and C. owczarzaki. We further showed that the function of CEBPα to drive phagocyte program in nonphagocytic blood cells has been conserved in tunicate, sponge, and C. owczarzaki. We finally showed that, in murine hematopoiesis, repression of CEBPα to maintain nonphagocytic lineages is commonly achieved by polycomb complexes. These findings indicate that the initial blood cells emerged inheriting a unicellular organism program driven by CEBPα and that the program has also been seamlessly inherited in phagocytes of various animal species throughout evolution.

On the origin of the functional versatility of macrophages

“…Regarding the origin of macrophage functional versatility, the effort requires tracing macrophage characteristic features in evolution. Recent work conducted by Nagahata and colleagues, which, on the genetic level, supports the hypotheses that many functions typical of bactericidal macrophages evolved from a common ancestor of animals, and that many characteristic macrophage features are adaptations of free-living unicellular bacterivorous amoebae (Nagahata et al, 2022;Rayamajhee et al, 2022).…”

Emergence of Slc11 clade MCbgut: a parsimonious hypothesis for the dawn of Lactobacillales in the gut of early vertebrates

“…According to these views, gut LB and SCFA producers and their metabolites could directly instruct the emerging adaptive immune system while sustaining systemic innate immunity, due to Firmicutes intrinsic lysozyme sensitivity [77]. Also, both lymphocyte and erythrocyte cell types emerged as vertebrate-specificities [78]. Duodenal Fe absorption boosted with gastric acidification likely helped developing the erythron (e.g., heterotetrameric hemoglobin in jawed vertebrates, [79]) to distribute oxygen within tissues and sustain their metabolic activity.…”

“…Also, both lymphocyte and erythrocyte cell types emerged as vertebrate-specificities [78]. Duodenal Fe absorption boosted with gastric acidification likely helped developing the erythron (e.g., hetero-tetrameric hemoglobin in jawed vertebrates, [79]) to distribute oxygen within tissues and sustain their metabolic activity.…”

Both Horatio and Polonius: Innate Lymphoid Cells in Tissue Homeostasis and Repair

“…Unconventional innate-like lymphocytes also share similar developmental signatures to ILCs, such as expression of the TF PLZF ( 7 ); have a restricted repertoire of Ig gene rearrangement; and frequently exhibit long-term tissue residence with poised effector function. We propose that further studies rooted in comparative evolutionary analyses and developmental ontogeny of lymphocytes will be essential in deciphering how danger and stress signal recognition arose in ILCs, because similar approaches have been fruitful in understanding TCRα diversity ( 45 ) and the animal ancestry of hematopoietic cells ( 46 ).…”