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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

idney organoids recapitulate human basement membrane assembly in health and diseas

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Author(s):
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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]
Total Authors: 13
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
Total Affiliations: 9
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