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Oral Sessions
Day 3, June 24（Tue.） 12:25-12:40
Room B (Maesato Center)
- 3B-O1-1225
Targeted spatial metabolomics and transcriptomics for mapping metabolism in the human lung
(1Karolinska Institute, 2Stockholm University, 3Karolinska University Hospital)
Matthew Smith1, Jesper Säfholm1,3, Alexandra Firsova2, Christos Samakovlis2, oCraig Wheelock1,3
Asthma is characterized by chronic inflammation in the lung that is mediated by a combination of immune and structural cells. These different cell populations produce multiple metabolites that impact asthma pathogenesis. We developed a multi-modal method to perform combined targeted mass spectrometry imaging (MSI) and targeted spatial transcriptomics to determine the spatial heterogeneity of metabolism in human lung tissue. Distal lung explants were obtained post-excision from patients undergoing lobectomies and challenged ex vivo. Metabolite distribution was mapped using desorption electrospray ionization (DESI) with targeted multiple-reaction-monitoring (MRM) mass spectrometry. Single-Cell Resolution IN Situ Hybridization On Tissues (SCRINSHOT) was subsequently conducted on the same cryosection to map RNA and profile cellular niches. We developed an open-source workflow to process metabolite ion images from DESI-MRM data (quantMSImageR), annotate anatomical and cellular regions (CellProfiler) and map the annotations between ion and microscope images of different spatial resolutions and acquisition areas (napari based tools). This multi-modal workflow was able to sequentially co-register metabolites and RNA distributions from the same cryosection, enabling visualization of metabolic and cellular responses to ex vivo challenges. This integrated workflow provides routine visualization of the metabolite distribution and associated cell type, enabling novel insights into biochemical processes in the lung.