JOM KITA KE POLITEKNIK
Image from Google Jackets

Adult human kidney organoids originate from CD24(+) cells and represent an advanced model for adult polycystic kidney disease

By: Contributor(s): Publication details: 2022-11.Subject(s): Genre/Form: Online resources: Summary: Adult kidney organoids have been described as strictly tubular epithelial and termed tubuloids. While the cellular origin of tubuloids has remained elusive, here we report that they originate from a distinct CD24(+) epithelial subpopulation. Long-term-cultured CD24(+)-derived tubuloids represent a functional human kidney tubule. We show that kidney tubuloids can be used to model the most common inherited kidney disease, namely autosomal dominant polycystic kidney disease (ADPKD), reconstituting the phenotypic hallmark of this disease with cyst formation. Single-cell RNA sequencing of CRISPR/Cas9 gene-edited PKD1 and PKD2 knockout tubuloids and human ADPKD and control tissue show similarities in upregulation of disease-driving genes. Furthermore, in a proof of concept, we demonstrate that tolvaptan, the only approved drug for ADPKD, shows a significant effect on cyst size in tubuloids but no effect in a pluripotent-stem-cell-derived model. Thus, tubuloids derive from a tubular epithelial subpopulation and represent an advanced model for ADPKD disease modeling.
Item type:
Tags from this library: No tags from this library for this title. Log in to add tags.
Star ratings
    Average rating: 0.0 (0 votes)
No physical items for this record

/pmc/articles/PMC7613830/

/pubmed/36303074

Adult kidney organoids have been described as strictly tubular epithelial and termed tubuloids. While the cellular origin of tubuloids has remained elusive, here we report that they originate from a distinct CD24(+) epithelial subpopulation. Long-term-cultured CD24(+)-derived tubuloids represent a functional human kidney tubule. We show that kidney tubuloids can be used to model the most common inherited kidney disease, namely autosomal dominant polycystic kidney disease (ADPKD), reconstituting the phenotypic hallmark of this disease with cyst formation. Single-cell RNA sequencing of CRISPR/Cas9 gene-edited PKD1 and PKD2 knockout tubuloids and human ADPKD and control tissue show similarities in upregulation of disease-driving genes. Furthermore, in a proof of concept, we demonstrate that tolvaptan, the only approved drug for ADPKD, shows a significant effect on cyst size in tubuloids but no effect in a pluripotent-stem-cell-derived model. Thus, tubuloids derive from a tubular epithelial subpopulation and represent an advanced model for ADPKD disease modeling.

https://www.springernature.com/gp/open-research/policies/accepted-manuscript-termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms

en

There are no comments on this title.

to post a comment.