Reference

Walter W., Alonso-Herranz L., Trappetti V., Crespo I., Ibberson M., Cedenilla M., Karaszewska A., Núñez V., Xenarios I., Arroyo A.G., Sanchez-Cabo F., Ricote M. Deciphering the dynamic transcriptional and post-transcriptional networks of cardiac macrophages in the healthy heart and after myocardial injury. Cell reports. 2018 Apr 10;23(2):622-636. Cover Cell Reports 100418

Authors

Wencke Walter*, Laura Alonso-Herranz*, Verdiana Trappetti, Isaac Crespo, Mark Ibberson, Marta Cedenilla, Anna Karaszewska, Vanessa Núñez, Ioannis Xenarios, Alicia G. Arroyo, Fátima Sánchez-Cabo, and Mercedes Ricote. *These authors contributed equally.

Abstract

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 Il10. 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.

 

Description

Our group is interested in the behavior and transcriptional regulation of macrophages in the context of complex disease environments. We have generated a whole transcriptome dataset (mRNA, miRNA, and lincRNA) of macrophages in the healthy heart and at different stages post-injury, providing an important resource for improving understanding of how macrophages integrate, process, and respond to signals from their local environment.

 

 

CNIC 006

 

REFERENCIA DEL GRUPO INVESTIGADOR

El grupo dirigido por la Dra. Mercedes Ricote se centra en el estudio de la función y regulación transcripcional de los macrófagos en homeostasis y en enfermedades inflamatorias. Los macrófagos son células del sistema inmune presentes en prácticamente todos los tejidos, contribuyendo a su desarrollo, homeostasis, protección frente a patógenos y reparación del daño tisular. Nuestro grupo tiene un interés especial en estudiar la contribución de los macrófagos a la reparación cardiaca que tiene lugar en respuesta al infarto de miocardio, con el objetivo de utilizarlos como dianas terapéuticas en el tratamiento de enfermedades metabólicas y cardiovasculares.

 Descargar el artículo 

Did you publish an interesting article recently?

Send it through our application form and we will contact you. Age limit: 32.

The selected articles will participate at the Award to the best article of young people of the SEBBM which will be given during SEBBM conference, that will take place at Spain (free registration, travel and accommodation).

More articles of the month

Evaluation of different approaches used to study membrane permeabilization by actinoporins on model lipid vesicles

30-07-2020

Release of aqueous contents from model lipid vesicles has been a standard procedure to evaluate pore formation efficiency by actinoporins, such as sticholysin II (StnII), for the last few decades...

Read more

ADAR1-mediated RNA editing is a novel oncogenic process in thyroid cancer and regulates miR-200 activity

01-07-2020

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA. A-to-I editing of RNA is a widespread posttranscriptional process that has recently emerged as an important mechanism...

Read more

Sarcoplasmic reticulum Ca2+ decreases with age and correlates with the decline in muscle function in Drosophila

29-05-2020

Sarcopenia, the loss of muscle mass and strength associated with age, has been linked to impairment of the cytosolic Ca2+ peak that triggers muscle contraction, but mechanistic details remain unknown...

Read more

Structural basis for substrate specificity and catalysis of α1,6-fucosyltransferase

30-04-2020

Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans. A single human enzyme α1,6-fucosyltransferase (FUT8) is the...

Read more

Molecular basis for fibroblast growth factor 23 O-glycosylation by GalNAc-T3

31-03-2020

Polypeptide GalNAc-transferase T3 (GalNAc-T3) regulates fibroblast growth factor 23 (FGF23) by O-glycosylating Thr178 in a furin proprotein processing motif RHT 178R ↓S. FGF23 regulates phosphate homeostasis and deficiency in GALNT3...

Read more

Identification of distinct maturation steps involved in human 40S ribosomal subunit biosynthesis

29-02-2020

Technical problems intrinsic to the purification of preribosome intermediates have limited our understanding of ribosome biosynthesis in humans. Addressing this issue is important given the implication of this biological process...

Read more

Unraveling the cellular origin and clinical prognostic markers of infant B-cell acute lymphoblastic leukemia using genome-wide analysis

23-01-2020

B-cell acute lymphoblastic leukemia is the commonest childhood cancer. In infants, B-cell acute lymphoblastic leukemia remains fatal, especially in patients with t(4;11), present in ~80% of cases. The pathogenesis of...

Read more

Mip6 binds directly to the Mex67 UBA domainto maintain low levels of Msn2/4 stress-dependent mRNAs

23-12-2019

RNA-binding proteins (RBPs) participate in all steps of gene expression, underscoring their potential as regulators of RNA homeostasis. We structurally and functionally characterize Mip6, a four-RNA recognition motif (RRM)-containing RBP...

Read more

A bacterial light response reveals an orphan desaturase for human plasmalogen synthesis

01-12-2019

Plasmalogens are glycerophospholipids with a hallmark sn-1 vinyl ether bond. These lipids are found in animals and some bacteria and have proposed membrane organization, signaling, and antioxidant roles. We discovered...

Read more

The structure of a polygamous repressor reveals how phage-inducible chromosomal islands spread in nature

01-11-2019

Stl is a master repressor encoded by Staphylococcus aureus pathogenicity islands (SaPIs) that maintains integration of these elements in the bacterial chromosome. After infection or induction of a resident helper...

Read more

Protector Members