Kidney organoids recapitulate human basement membrane assembly in health and disease.
Elife
; 112022 01 25.
Article
en En
| MEDLINE
| ID: mdl-35076391
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Membrana Basal
/
Organoides
/
Riñón
/
Enfermedades Renales
Límite:
Animals
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Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Elife
Año:
2022
Tipo del documento:
Article
País de afiliación:
Reino Unido