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

Autor: David Finkle, Megan Smith, Denise M. Imai, Nicholas Bernstein, Baby Martin-McNulty, Margaret Ann Roy, Vladimir Jojic, Nimrod D. Rubinstein, Kevin M. Wright, Nicole L. Fong, Rochelle Buffenstein, Hugo G. Hilton, Peter Janki, Andrea T. Ireland
Rok vydání: 2019
Předmět:
0301 basic medicine
Physiology
Neutrophils
Cellular differentiation
Cell
Gene Expression
NK cells
Mice
0302 clinical medicine
Short Reports
Immune Physiology
Cellular types
Medicine and Health Sciences
Biology (General)
Mammals
Genome
Mammalian Genomics
biology
General Neuroscience
Immune cells
Eukaryota
Genomics
Animal Models
Naked Mole Rats
Biological Evolution
Cell biology
Immunosurveillance
medicine.anatomical_structure
Experimental Organism Systems
Vertebrates
White blood cells
Single-Cell Analysis
General Agricultural and Biological Sciences
Blood cells
QH301-705.5
Longevity
Immunology
Research and Analysis Methods
Rodents
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Immune system
Immunity
medicine
Genetics
Gene family
Animals
Molecular Biology Techniques
Molecular Biology
Naked mole-rat
Comparative genomics
General Immunology and Microbiology
Sequence Analysis
RNA
Mole Rats
Organisms
Computational Biology
Biology and Life Sciences
Marker Genes
biology.organism_classification
030104 developmental biology
Animal cells
Animal Genomics
Amniotes
Animal Studies
Transcriptome
030217 neurology & neurosurgery
Spleen
Zdroj: PLoS Biology
PLoS Biology, Vol 17, Iss 11, p e3000528 (2019)
ISSN: 1545-7885
Popis: 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.
A single-cell transcriptomic study of the immune system of the cancer-resistant naked mole-rat reveals that this animal lacks natural killer (NK) cells, thought to be crucial for cancer resistance. In contrast to dramatically expanded NK cell receptor and MHC-I gene families in human and mouse genomes, the naked mole-rat genome lacks the expansion of NK cell receptor genes and only has two MHC-I genes.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje