idney organoids recapitulate human basement membrane assembly in health and diseas

Author(s):Show less -

Morais, Mychel R. P. T. ^[1] ; Tian, Pinyuan ^[1] ; Lawless, Craig ^[1] ; Murtuza-Baker, Syed ^[2] ; Hopkinson, Louise ^[1] ; Woods, Steven ^[3] ; Mironov, Aleksandr ^[4] ; Long, David A. ^[5] ; Gale, Daniel P. ^[6] ; Zorn, Telma M. T. ^[7] ; Kimber, Susan J. ^[3] ; Zent, Roy ^[8] ; Lennon, Rachel ^{[1, 9]}

Affiliation

^[1] Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester, Lancs - England

^[2] Univ Manchester, Div Informat Imaging & Data Sci, Manchester, Lancs - England

^[3] Univ Manchester, Div Cell Matrix Biol & Regenerat Med, Manchester, Lancs - England

^[4] Univ Manchester, Electron Microscopy Core Facil, Manchester, Lancs - England

^[5] UCL, Dev Biol & Canc Programme, London - England

^[6] UCL, Dept Renal Med, London - England

^[7] Univ Sao Paulo, Dept Cell & Dev Biol, Sao Paulo - Brazil

^[8] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN - USA

^[9] Manchester Univ Hosp NHS Fdn Trust, Royal Manchester Childrens Hosp, Dept Paediat Nephrol, Manchester, Lancs - England

• Document type: Journal article
• Source: eLIFE; v. 11, JAN 25 2022.
• Web of Science Citations: 0

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 organoid BM assembly and provide a platform for understanding its wider relevance in human development and disease. (AU)

• FAPESP's process: 17/26785-5 - Global analysis of enriched glomerular extracellular matrix of pre-term foetuses of normoglycemic and hyperglycaemic mothers using mass spectrometry-based proteomics
• Grantee: Mychel Raony Paiva Teixeira Morais
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate