Single-cell transcriptomics of the naked mole-rat reveals unexpected features of mammalian immunity.

Autor: Hilton HG; Calico Life Sciences LLC, South San Francisco, California, United States of America., Rubinstein ND; Calico Life Sciences LLC, South San Francisco, California, United States of America., Janki P; Calico Life Sciences LLC, South San Francisco, California, United States of America., Ireland AT; Calico Life Sciences LLC, South San Francisco, California, United States of America., Bernstein N; Calico Life Sciences LLC, South San Francisco, California, United States of America., Fong NL; Calico Life Sciences LLC, South San Francisco, California, United States of America., Wright KM; Calico Life Sciences LLC, South San Francisco, California, United States of America., Smith M; Calico Life Sciences LLC, South San Francisco, California, United States of America., Finkle D; Calico Life Sciences LLC, South San Francisco, California, United States of America., Martin-McNulty B; Calico Life Sciences LLC, South San Francisco, California, United States of America., Roy M; Calico Life Sciences LLC, South San Francisco, California, United States of America., Imai DM; Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America., Jojic V; Calico Life Sciences LLC, South San Francisco, California, United States of America., Buffenstein R; Calico Life Sciences LLC, South San Francisco, California, United States of America.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2019 Nov 21; Vol. 17 (11), pp. e3000528. Date of Electronic Publication: 2019 Nov 21 (Print Publication: 2019).
DOI: 10.1371/journal.pbio.3000528
Abstrakt: The immune system comprises a complex network of specialized cells that protects against infection, eliminates cancerous cells, and regulates tissue repair, thus serving a critical role in homeostasis, health span, and life span. The subterranean-dwelling naked mole-rat (NM-R; Heterocephalus glaber) exhibits prolonged life span relative to its body size, is unusually cancer resistant, and manifests few physiological or molecular changes with advancing age. We therefore hypothesized that the immune system of NM-Rs evolved unique features that confer enhanced cancer immunosurveillance and prevent the age-associated decline in homeostasis. Using single-cell RNA-sequencing (scRNA-seq) we mapped the immune system of the NM-R and compared it to that of the short-lived, cancer-prone mouse. In contrast to the mouse, we find that the NM-R immune system is characterized by a high myeloid-to-lymphoid cell ratio that includes a novel, lipopolysaccharide (LPS)-responsive, granulocyte cell subset. Surprisingly, we also find that NM-Rs lack canonical natural killer (NK) cells. Our comparative genomics analyses support this finding, showing that the NM-R genome lacks an expanded gene family that controls NK cell function in several other species. Furthermore, we reconstructed the evolutionary history that likely led to this genomic state. The NM-R thus challenges our current understanding of mammalian immunity, favoring an atypical, myeloid-biased mode of innate immunosurveillance, which may contribute to its remarkable health span.
Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: NDR, ATI, NB, NLF, KMW, MS, BM-M, MR, VJ, RB, HGH, PJ, and DF were employees of Calico Life Sciences at the time that the study was undertaken.
Databáze: MEDLINE
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