The team has been working on radiation-induced
pulmonary fibrosis for several years and has introduced state-of-the-art
technologies such as single cell (sc) RNAseq and single molecule (sm) FISH to
the study of the cellular and molecular mechanisms that lead to failure in the
regeneration response of the irradiated lung. We use a well characterized mouse
model, have sequenced almost half a million lung cells and collected data
corresponding to several time points after irradiation under conditions that
lead (or not, as a control) to irreversible lung fibrosis.
We have also access to human specimens of
irradiated lungs, which should allow us to facilitate results extrapolations.
Our data has revealed previously unrecognized events affecting capillary
endothelial cells. We have also data pointing to fibrosis-specific response
involving resident macrophage cells. Specifically, transcriptional signatures
can be detected involving both inflammatory and anti-inflammatory pathways, as
well as the implication of ligand production that potentially target other cell
In this project, we will use available
genetically modified mice to determine the role of lung resident myeloid
populations in response to radiation.
We propose to:
characterise, by scRNAseq analysis, the molecular alterations
induced by radiation in the different subsets of lung myeloid cells
map, by smFISH-based spatial transcriptomic approaches,
interesting subsets of lung macrophages or dendritic cells that may play a role
in the development of radiation-induced pulmonary fibrosis
select, from the scRNAseq data, putative interactions between
resident myeloid cells and other lung cell types that will be validated by in
vitro functional assays.