idney organoids recapitulate human basement membra... - BV FAPESP
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idney organoids recapitulate human basement membrane assembly in health and diseas

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Autor(es):
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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]
Número total de Autores: 13
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 9
Tipo de documento: Artigo Científico
Fonte: eLIFE; v. 11, JAN 25 2022.
Citações Web of Science: 0
Resumo

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)

Processo FAPESP: 17/26785-5 - Análise global da matriz extracelular glomerular enriquecida de fetos pré-termo de mães normoglicêmicas e hiperglicêmicas usando espectrometria de massas aplicada à análise proteômica
Beneficiário:Mychel Raony Paiva Teixeira Morais
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado