Targeting fibroblast-endothelial interactions in LAM pathogenesis using 3D spheroid models and spatial transcriptomics

This study was supported by the Hastings Foundation (ALR) , The LAM Foundation (ALR, LAM0154SG01-22-891077) , the German Research Foundation (SKG, KO5803/2-1) , the German Federal Ministry of Education (SKG, 01EO2102) , and the NIH/National Heart, Lung, and Blood Institute (VPK, R01HL141462, R01HL158737, R01151647, and U01HL131022) . Mariah Leidinger, Comparative Pathology Core, University of Iowa, prepared the tissue samples for spatialomics processing. Visium data presented herein were obtained at the Iowa NeuroBank Core in the INI and the Genomics Division in the IIHG. Initial data processing and analysis were carried out by the Bioinformatics Division in the IIHG. INI is supported by the Roy J. Carver Charitable Trust and the University of Iowa Carver College of Medicine. IIHG is supported, in part, by the University of Iowa Carver College of Medicine. Opal staining was performed in collaboration with the Translational Pathology Core Laboratory in the Department of Pathology and Laboratory Medicine at the UCLA David Geffen School of Medicine. The authors would like to acknowledge use of the University of Iowa Central Microscopy Research Facility, a core resource supported by the University of Iowa Vice President for Research and the Carver College of Medicine. The use of the ZEISS LSM 710 confocal microscope was supported by a Shared Instrumentation grant from the NIH under award number S10 RR025439-01. Finally, the authors would like to thank the Center for Gene Therapy Cell and Tissue Core, supported by NIH P30DK054759-22; the Cystic Fibrosis Foundation Tissue Procurement and Cell Culture Core at University of North Carolina at Chapel Hill, supported by CF BOUCE19R; and the NIH Cystic Fibrosis Research and Translation Core Center Cell Models Core at University of North Carolina at Chapel Hill, supported by NIH P30DK065988.