%0 Journal Article %A Mychel Raony Paiva Teixeira Morais %A Pinyuan Tian %A Craig Lawless %A Syed Murtuza-Baker %A Louise Hopkinson %A Steven Woods %A Aleksandr Mironov %A David Andrew Long %A Daniel Gale %A Telma Maria Tenorio Zorn %A Susan Kimber %A Roy Zent %A Rachel Lennon %T Kidney organoids: A system to study human basement membrane assembly in health and disease %D 2021 %R 10.1101/2021.06.27.450067 %J bioRxiv %P 2021.06.27.450067 %X Basement membranes (BMs) are complex macromolecular networks underlying all continuous layers of cells. Essential components include type IV collagen and laminins, which are affected by human genetic defects 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 vertebrate BM assembly and provide a platform for understanding its wider relevance in human development and disease.Competing Interest StatementThe authors have declared no competing interest. %U https://www.biorxiv.org/content/biorxiv/early/2021/06/29/2021.06.27.450067.full.pdf