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Modeling the evolutionary history of nonclassical monocytes in mammals

Daniel J. Araujo, Diego Fernandez, Ahmad Alimadadi, Axel Zagal-Norman, Catherine C. Hedrick
doi: https://doi.org/10.1101/2022.10.12.511958
Daniel J. Araujo
1Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, CA
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Diego Fernandez
1Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, CA
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Ahmad Alimadadi
1Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, CA
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Axel Zagal-Norman
1Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, CA
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Catherine C. Hedrick
1Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, CA
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  • For correspondence: hedrick@lji.org
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ABSTRACT

The immune system has experienced major changes in both its organization and function during the evolution of tetrapod animals. Still, the ancestry of specific cell types and the historical relationships between modern immune cells has received little attention. While all tetrapods possess mononuclear blood cells and monocytes, vasculature-patrolling nonclassical monocytes (CD16+CD14- in humans, Ly6C- in mice) have so far only been described in mammals. The question of whether nonclassical monocytes are specific to the mammalian lineage has not been answered. Cell types can be described as traits that persist via the inheritance of core regulatory complexes of transcription factors. We utilized transcriptional network analyses on a human monocyte single-cell RNA-sequencing dataset to highlight the core regulatory complex associated with nonclassical monocyte production (nCoRC). We then applied BLAST-based analyses to quantify the conservation of human nCoRC members amongst mammals and nonmammals. We determined that the average sequence similarity of nCoRC members is highest amongst mammals and that such conservation is not observed in non-mammalian tetrapods. We also discovered that this sequence similarity is specifically driven by boreoeutherian placental mammals. Finally, we found the receptor proteins upstream of nonclassical monocyte assembly are also more homologous in mammals than non-mammals. This work provides an evolutionary model in which the capacity for nonclassical monocyte production is unique to the mammalian lineage.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Cite as: Araujo DJ, Fernandez D, Alimadadi A, Zagal-Norman A, and Hedrick CC. Modeling the evolutionary history of nonclassical monocytes in mammals. Under preparation.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 17, 2022.
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Modeling the evolutionary history of nonclassical monocytes in mammals
Daniel J. Araujo, Diego Fernandez, Ahmad Alimadadi, Axel Zagal-Norman, Catherine C. Hedrick
bioRxiv 2022.10.12.511958; doi: https://doi.org/10.1101/2022.10.12.511958
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Modeling the evolutionary history of nonclassical monocytes in mammals
Daniel J. Araujo, Diego Fernandez, Ahmad Alimadadi, Axel Zagal-Norman, Catherine C. Hedrick
bioRxiv 2022.10.12.511958; doi: https://doi.org/10.1101/2022.10.12.511958

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