Objective Neutrophils follow daily cycles of release from and migration back into the bone marrow, where they are eliminated. After searching for the presence of neutrophils across multiple tissues of healthy mice under steady state, my host laboratory found neutrophils in most of the tissue analyzed. These findings require the study of the role of neutrophils in their tissue of destination. Several studies have shown that neutrophil clearance might be a significant source of homeostatic signals able to functionally modulate the tissues and organs where they are eliminated. In addition, specific functions for neutrophils in the spleen have already been described. I hypothesize that neutrophils may have important roles for the homeostasis and functioning of the tissues that they infiltrate, and that they acquire tissue-specific phenotypes that favor their local functions.To understand neutrophil homeostatic functions within the tissue, I will first characterize the transcriptome of 7 different subsets of neutrophils population from intestine, lung, muscle, skin, spleen, blood and bone marrow by RNA-sequencing. In addition, to investigate weather neutrophil heterogeneity within the tissues is a stochastic or a tissue-educated mechanism I will perform single cell RNA sequencing (sc-RNA-seq) of blood neutrophils to characterize the presence of a neutrophil tissue-specific signature in the blood. Moreover, I will combine next generation sequencing techniques with the use of different transgenic mouse models to uncover tissue specific regenerative functions of neutrophils in the skeletal muscle and the skin. Results obtained in this proposal aim to challenge the classical conception about neutrophils as a homogenous population of terminally differentiated cells with functions restricted to inflammation and to explore their hetroogeneity and expand our knowledge about their specific functions during tissue homeostasis. Fields of science medical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicineimmunologyautoimmune diseasesmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineneurologystrokemedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2016 - Individual Fellowships Call for proposal H2020-MSCA-IF-2016 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) Net EU contribution € 158 121,60 Address Calle melchor fernandez almagro 3 28029 Madrid Spain See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
