SiglecF(HI) Marks Late-Stage Neutrophils of the Infarcted Heart: A Single-Cell Transcriptomic Analysis of Neutrophil Diversification

Autor: Aaron D. Aguirre, Van Kim Ninh, Zhenxing Fu, Claire Zhang, Joan Heller Brown, Kevin R. King, David M Calcagno, Shigeki Miyamoto, Avinash Toomu, Kenneth Huang
Rok vydání: 2021
Předmět:
Neutrophils
Cell
Myocardial Infarction
heart
Diversification (marketing strategy)
Granulopoiesis
Transcriptome
03 medical and health sciences
Mice
0302 clinical medicine
neutrophil maturity
single‐cell RNA sequencing
medicine
Diseases of the circulatory (Cardiovascular) system
Animals
Myocardial infarction
030304 developmental biology
Original Research
Sialic Acid Binding Immunoglobulin-like Lectins
Inflammation
0303 health sciences
granulopoiesis
business.industry
Sequence Analysis
RNA
Myocardium
Late stage
medicine.disease
siglecF
Mice
Inbred C57BL
Disease Models
Animal
medicine.anatomical_structure
RC666-701
030220 oncology & carcinogenesis
Immunology
Infarcted heart
Single-Cell Analysis
Cardiology and Cardiovascular Medicine
business
Basic Science Research
Health Services and Outcomes Research
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 4 (2021)
ISSN: 2047-9980
Popis: Background Neutrophils are thought to be short‐lived first responders to tissue injuries such as myocardial infarction (MI), but little is known about their diversification or dynamics. Methods and Results We permanently ligated the left anterior descending coronary arteries of mice and performed single‐cell RNA sequencing and analysis of >28 000 neutrophil transcriptomes isolated from the heart, peripheral blood, and bone marrow of mice on days 1 to 4 after MI or at steady‐state. Unsupervised clustering of cardiac neutrophils revealed 5 major subsets, 3 of which originated in the bone marrow, including a late‐emerging granulocyte expressing SiglecF, a marker classically used to define eosinophils. SiglecF HI neutrophils represented ≈25% of neutrophils on day 1 and grew to account for >50% of neutrophils by day 4 post‐MI. Validation studies using quantitative polymerase chain reaction of fluorescent‐activated cell sorter sorted Ly6G + SiglecF HI and Ly6G + SiglecF LO neutrophils confirmed the distinct nature of these populations. To confirm that the cells were neutrophils rather than eosinophils, we infarcted GATA‐deficient mice (∆dblGATA) and observed similar quantities of infiltrating Ly6G + SiglecF HI cells despite marked reductions of conventional eosinophils. In contrast to other neutrophil subsets, Ly6G + SiglecF HI neutrophils expressed high levels of Myc‐regulated genes, which are associated with longevity and are consistent with the persistence of this population on day 4 after MI. Conclusions Overall, our data provide a spatial and temporal atlas of neutrophil specialization in response to MI and reveal a dynamic proinflammatory cardiac Ly6G + SigF + (Myc + NFϰB + ) neutrophil that has been overlooked because of negative selection.
Databáze: OpenAIRE
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