Abstract
Basement membranes (BMs) are complex macromolecular networks underlying all continuous layers of cells. Essential components include collagen IV and laminins, which are affected by human genetic variants leading to a range of debilitating conditions including kidney, muscle, and cerebrovascular phenotypes. We investigated the dynamics of BM assembly in human pluripotent stem cell-derived kidney organoids. We resolved their global BM composition and discovered a conserved temporal sequence in BM assembly that paralleled mammalian fetal kidneys. We identified the emergence of key BM isoforms, which were altered by a pathogenic variant in COL4A5. Integrating organoid, fetal and adult kidney proteomes we found dynamic regulation of BM composition through development to adulthood, and with single-cell transcriptomic analysis we mapped the cellular origins of BM components. Overall, we define the complex and dynamic nature of kidney BM assembly and provide a platform for understanding its wider relevance in human development and disease.
Original language | English |
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Journal | eLife |
Volume | 11 |
Early online date | 25 Jan 2022 |
DOIs | |
Publication status | Published - 25 Jan 2022 |
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Biological Mass Spectrometry (BioMS) Facility
Knight, D. (Platform Lead), Warwood, S. (Senior Technical Specialist), Selley, J. (Technical Specialist), Taylor, G. (Technical Specialist), Fullwood, P. (Technical Specialist), Keevill, E.-J. (Senior Technician) & Allsey, J. (Technician)
FBMH Platform Sciences, Enabling Technologies & InfrastructureFacility/equipment: Facility