期刊
CELL REPORTS
卷 23, 期 2, 页码 622-636出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.03.029
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资金
- Spanish Ministry of Economy and Competitiveness [SAF2015-64287R, SAF2015-71878-REDT]
- Fundacion Marato TV3 [121931]
- European Commission FP7 [CardioNext-ITN-608027]
- La Caixa-CNIC
- MEIC
- Pro CNIC Foundation
- Severo Ochoa Center of Excellence (MEIC award) [SEV-2015-0505]
Macrophage plasticity has been studied in vitro, but transcriptional regulation upon injury is poorly understood. We generated a valuable dataset that captures transcriptional changes in the healthy heart and after myocardial injury, revealing a dynamic transcriptional landscape of macrophage activation. Partial deconvolution suggested that post-injury macrophages exhibit overlapping activation of pro-inflammatory and anti-inflammatory programs rather than aligning to canonical M1/M2 programs. Furthermore, simulated dynamics and experimental validation of a regulatory core of the underlying gene-regulatory network revealed a negative-feedback loop that limits initial inflammation via hypoxia-mediated upregulation of ll10. Our results also highlight the prominence of post-transcriptional regulation (miRNAs, mRNA decay, and lincRNAs) in attenuating the myocardial injury-induced inflammatory response. We also identified a cardiac-macrophage-specific gene signature (e.g., Egfr and Lifr) and time-specific markers for macrophage populations (e.g., Lyve1, Cd40, and Mrc1). Altogether, these data provide a core resource for deciphering the transcriptional network in cardiac macrophages in vivo.
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