Pathology Research

Experimental Vascular Pathology PhD candidate Renée Tillie recently attended the International Vascular Biology Meeting in Oakland, San Francisco Bay Area, USA. 
She submitted an abstract about her work on fibroblast heterogeneity in healthy and diseased vasculature. Out of many, her abstract was chosen for an oral presentation. Additionally, she received two travel awards, one from the North American Vascular Biology Organization, and one from the MDPI Journal of Cardiovascular Development and Disease.

Cells often adopt different phenotypes that are dictated by tissue-specific or local signals (such as cell-cell and cell-matrix contacts or the molecular micro-environment). This holds in extremis for macrophages, with their notoriously high phenotypic plasticity. Their broad range of functions, some even opposing, reflects their heterogeneity, and a multitude of subsets has already been described in different tissues or often even within the same tissue. Upon disease and the accompanying appearance of additional signals, this heterogeneity becomes even more complex.

The effect of the local micro-environment on macrophage phenotypes cannot be adequately studied by single-cell applications such as scRNAseq or cytometry, as these require cells to be detached from their context, while histology-based assessment lacks the phenotypic depth due to limitations in marker combination. A newly-developped 15-plex multispectral imaging approach allows for cell and subset classification based on multi-marker expression patterns. Integrating this information with additional measurements (such as mass spectrometry imaging performed at M4I) not only allows to map macrophage heterogeneity over the tissue but also to link the location of phenotypes to specific cellular, molecular and metabolic niches in complex tissue. The power of this approach was illustrated for macrophage subsets and their associated lipid signatures in murine atherosclerotic plaques.

Goossens P, Lu C, Cao J, Gijbels MJ, Karel JMH, Wijnands E, Claes BSR, Fazzi GE, Hendriks TFE,Wouters K, Smirnov E, van Zandvoort MJM, Balluff B, Cuypers E, Donners MMPC, Heeren RMA,Biessen EAL. Integrating multiplex immunofluorescent and mass spectrometry imaging to map myeloid heterogeneity in its metabolic and cellular context. Cell Metab. 2022 Jul 12:S1550-4131(22)00232-7. doi: 10.1016/j.cmet.2022.06.012. Epub ahead of print. PMID: 35858629.

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