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

Yosuke Nagahata, Kyoko Masuda, Yuji Nishimura, Tomokatsu Ikawa, Shinpei Kawaoka, Toshio Kitawaki, Yasuhito Nannya, Seishi Ogawa, Hiroshi Suga, Yutaka Satou, Akifumi Takaori-Kondo, Hiroshi Kawamoto

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Pages (from-to)2611-2625
Number of pages15
Issue number24
Publication statusPublished - 2022 Dec 15
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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