000 03774 am a22006613u 4500
042 _adc
100 1 0 _aXu, Yaoxian
_eauthor
_91567
700 1 0 _aKuppe, Christoph
_eauthor
_91568
700 1 0 _aPerales-Patón, Javier
_eauthor
_91569
700 1 0 _aHayat, Sikander
_eauthor
_91570
700 1 0 _aKranz, Jennifer
_eauthor
_91571
700 1 0 _aAbdallah, Ali T.
_eauthor
_91572
700 1 0 _aNagai, James
_eauthor
_91573
700 1 0 _aLi, Zhijian
_eauthor
_91574
700 1 0 _aPeisker, Fabian
_eauthor
_91575
700 1 0 _aSaritas, Turgay
_eauthor
_91576
700 1 0 _aHalder, Maurice
_eauthor
_91577
700 1 0 _aMenzel, Sylvia
_eauthor
_91578
700 1 0 _aHoeft, Konrad
_eauthor
_91579
700 1 0 _aKenter, Annegien
_eauthor
_91580
700 1 0 _aKim, Hyojin
_eauthor
_91581
700 1 0 _avan Roeyen, Claudia R. C.
_eauthor
_91582
700 1 0 _aLehrke, Michael
_eauthor
_91583
700 1 0 _aMoellmann, Julia
_eauthor
_91584
700 1 0 _aSpeer, Thimoteus
_eauthor
_91585
700 1 0 _aBuhl, Eva M.
_eauthor
_91586
700 1 0 _aHoogenboezem, Remco
_eauthor
_91587
700 1 0 _aBoor, Peter
_eauthor
_91588
700 1 0 _aJansen, Jitske
_eauthor
_91589
700 1 0 _aKnopp, Cordula
_eauthor
_91590
700 1 0 _aKurth, Ingo
_eauthor
_91591
700 1 0 _aSmeets, Bart
_eauthor
_91592
700 1 0 _aBindels, Eric
_eauthor
_91593
700 1 0 _aReinders, Marlies E. J.
_eauthor
_91594
700 1 0 _aBaan, Carla
_eauthor
_91595
700 1 0 _aGribnau, Joost
_eauthor
_91596
700 1 0 _aHoorn, Ewout J.
_eauthor
_91597
700 1 0 _aSteffens, Joachim
_eauthor
_91598
700 1 0 _aHuber, Tobias B
_eauthor
_91599
700 1 0 _aCosta, Ivan
_eauthor
_91600
700 1 0 _aFloege, Jürgen
_eauthor
_91601
700 1 0 _aSchneider, Rebekka K.
_eauthor
_91602
700 1 0 _aSaez-Rodriguez, Julio
_eauthor
_91603
700 1 0 _aFreedman, Benjamin S.
_eauthor
_91604
700 1 0 _aKramann, Rafael
_eauthor
_91605
245 0 0 _aAdult human kidney organoids originate from CD24(+) cells and represent an advanced model for adult polycystic kidney disease
260 _c2022-11.
500 _a/pmc/articles/PMC7613830/
500 _a/pubmed/36303074
520 _aAdult 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.
540 _a
540 _ahttps://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
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nNat Genet
856 4 1 _uhttp://dx.doi.org/10.1038/s41588-022-01202-z
_zConnect to this object online.
999 _c1982
_d1982