Delving deeper into the tissue proteome: improving cell-specificity with high spatial resolution MALDI-MS Imaging

MALDI-MS imaging (MALDI-MSI) is an analytical technique that enables to visualise the distribution and the relative intensity of analytes, including proteins, directly in tissue. Recent advancements in MALDI-MS instrumentation have led to the implementation of scanning lasers and consequent pixel sizes of less than 10 μm (rapifleXTM MALDI TissuetyperTM). However, in order to visualise the proteomic profiles of single cells, there are analytical limitations that must be overcome prior to this goal to be realised. Here, we summarise the most critical analytical steps that can limit the potential to obtain cell-specific profiles directly in situ. Following on from this, we highlight the added value of using high-spatial resolution MALDI-MSI in glomerulonephritis compared to the more routinely used spatial resolution (~ 50 μm). Briefly, it was possible to obtain specific protein profiles of the entire glomeruli, along with more specific, pathologically relevant, information from the individual cell types of the renal tissue. This higher degree of cell-specificity may enable the future detection of cell-specific markers implicated in the development and progression of renal disease.