Myeloid cell biology in tissue damage and inflammation
The lab is focused on unravelling heterogeneity within the mononuclear phagocyte compartment in health and disease in terms of both phenotype and function in mice and men. To do this, we use state of the art techniques including single cell RNA sequencing and 28-parameter flow cytometry alongside subset specific in vivo mouse models including the Clec4F-Cre to target Kupffer cells in the liver, the Xcr1-Cre to target cDC1s, the Fcgr1-Cre to target all macrophages and some new DRE-CRE tools currently being developed for LAMs. The team is especially interested in understanding this heterogeneity in the settings of liver disease and fibrosis such as metabolic dysfunction associated steatotic liver disease (MASLD). MASLD is currently one of the most significant clinical burdens in the western world and is thought to be the main reason for liver transplantation by 2030. Despite this there are no effective treatments currently available. As MNPs have been proposed to play a role in MASLD progression we hypothesize that correctly identifying and distinguishing between these cell subsets. Having recently identified the different subsets present using a range of multiomics technologies including single cell RNA-sequencing, single nuclei RNA-sequencing and spatial transcriptomics, we are now addressing the unique functions of each of these clusters using the existing and novel tools described above.
Areas of Expertise
- Identification of MNP subsets across tissues and species
- In vivo models of liver disease
- 28+ parameter flow cytometry
- Single cell technologies
- Spatial technologies
Technology Transfer Potential
- Identification and manipulation of relevant myeloid cell subsets in different disease settings
Selected publications
- Guilliams, M. et al. Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Cell 185, 379-396 (2022). Visit ➚
- Guilliams, M. & Scott, C. L. Liver macrophages in health and disease. Immunity 55, 1515-1529 (2022). Visit ➚
- Remmerie, A. et al. Osteopontin Expression Identifies a Subset of Recruited Macrophages Distinct from Kupffer Cells in the Fatty Liver. Immunity 53, 641-657 e614 (2020). Visit ➚
- Scott, C. L. et al. The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages. Immunity 49, 312-325 (2018). Visit ➚
- Scott, C. L. et al. Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells. Nat Commun 7, 10321 (2016). Visit ➚
Bibliography
- Full bibliography Visit ➚
