Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2hi macrophages in infarcted hearts.
Nat Commun
; 13(1): 4580, 2022 08 06.
Article
em En
| MEDLINE
| ID: mdl-35933399
ABSTRACT
Heart failure (HF) is a frequent consequence of myocardial infarction (MI). Identification of the precise, time-dependent composition of inflammatory cells may provide clues for the establishment of new biomarkers and therapeutic approaches targeting post-MI HF. Here, we investigate the spatiotemporal dynamics of MI-associated immune cells in a mouse model of MI using spatial transcriptomics and single-cell RNA-sequencing (scRNA-seq). We identify twelve major immune cell populations; their proportions dynamically change after MI. Macrophages are the most abundant population at all-time points (>60%), except for day 1 post-MI. Trajectory inference analysis shows upregulation of Trem2 expression in macrophages during the late phase post-MI. In vivo injection of soluble Trem2 leads to significant functional and structural improvements in infarcted hearts. Our data contribute to a better understanding of MI-driven immune responses and further investigation to determine the regulatory factors of the Trem2 signaling pathway will aid the development of novel therapeutic strategies for post-MI HF.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Insuficiência Cardíaca
/
Infarto do Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2022
Tipo de documento:
Article