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

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Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease. / Xu, Yaoxian; Kuppe, Christoph; Perales-Patón, Javier; Hayat, Sikander; Kranz, Jennifer; Abdallah, Ali T; Nagai, James; Li, Zhijian; Peisker, Fabian; Saritas, Turgay; Halder, Maurice; Menzel, Sylvia; Hoeft, Konrad; Kenter, Annegien; Kim, Hyojin; van Roeyen, Claudia R C; Lehrke, Michael; Moellmann, Julia; Speer, Thimoteus; Buhl, Eva M; Hoogenboezem, Remco; Boor, Peter; Jansen, Jitske; Knopp, Cordula; Kurth, Ingo; Smeets, Bart; Bindels, Eric; Reinders, Marlies E J; Baan, Carla; Gribnau, Joost; Hoorn, Ewout J; Steffens, Joachim; Huber, Tobias B; Costa, Ivan; Floege, Jürgen; Schneider, Rebekka K; Saez-Rodriguez, Julio; Freedman, Benjamin S; Kramann, Rafael.

In: NAT GENET, Vol. 54, No. 11, 11.2022, p. 1690-1701.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Xu, Y, Kuppe, C, Perales-Patón, J, Hayat, S, Kranz, J, Abdallah, AT, Nagai, J, Li, Z, Peisker, F, Saritas, T, Halder, M, Menzel, S, Hoeft, K, Kenter, A, Kim, H, van Roeyen, CRC, Lehrke, M, Moellmann, J, Speer, T, Buhl, EM, Hoogenboezem, R, Boor, P, Jansen, J, Knopp, C, Kurth, I, Smeets, B, Bindels, E, Reinders, MEJ, Baan, C, Gribnau, J, Hoorn, EJ, Steffens, J, Huber, TB, Costa, I, Floege, J, Schneider, RK, Saez-Rodriguez, J, Freedman, BS & Kramann, R 2022, 'Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease', NAT GENET, vol. 54, no. 11, pp. 1690-1701. https://doi.org/10.1038/s41588-022-01202-z

APA

Xu, Y., Kuppe, C., Perales-Patón, J., Hayat, S., Kranz, J., Abdallah, A. T., Nagai, J., Li, Z., Peisker, F., Saritas, T., Halder, M., Menzel, S., Hoeft, K., Kenter, A., Kim, H., van Roeyen, C. R. C., Lehrke, M., Moellmann, J., Speer, T., ... Kramann, R. (2022). Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease. NAT GENET, 54(11), 1690-1701. https://doi.org/10.1038/s41588-022-01202-z

Vancouver

Xu Y, Kuppe C, Perales-Patón J, Hayat S, Kranz J, Abdallah AT et al. Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease. NAT GENET. 2022 Nov;54(11):1690-1701. https://doi.org/10.1038/s41588-022-01202-z

Bibtex

@article{66db4be7e3dd401aa37835c71696d247,
title = "Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease",
abstract = "Adult kidney organoids have been described as strictly tubular epithelia 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+ cell-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 shows similarities in upregulation of disease-driving genes. Furthermore, in a proof of concept, we demonstrate that tolvaptan, the only approved drug for ADPKD, has a significant effect on cyst size in tubuloids but no effect on a pluripotent stem cell-derived model. Thus, tubuloids are derived from a tubular epithelial subpopulation and represent an advanced system for ADPKD disease modeling.",
keywords = "Adult, Humans, Polycystic Kidney, Autosomal Dominant/genetics, TRPP Cation Channels/genetics, Organoids, Kidney, Cysts, CD24 Antigen/genetics",
author = "Yaoxian Xu and Christoph Kuppe and Javier Perales-Pat{\'o}n and Sikander Hayat and Jennifer Kranz and Abdallah, {Ali T} and James Nagai and Zhijian Li and Fabian Peisker and Turgay Saritas and Maurice Halder and Sylvia Menzel and Konrad Hoeft and Annegien Kenter and Hyojin Kim and {van Roeyen}, {Claudia R C} and Michael Lehrke and Julia Moellmann and Thimoteus Speer and Buhl, {Eva M} and Remco Hoogenboezem and Peter Boor and Jitske Jansen and Cordula Knopp and Ingo Kurth and Bart Smeets and Eric Bindels and Reinders, {Marlies E J} and Carla Baan and Joost Gribnau and Hoorn, {Ewout J} and Joachim Steffens and Huber, {Tobias B} and Ivan Costa and J{\"u}rgen Floege and Schneider, {Rebekka K} and Julio Saez-Rodriguez and Freedman, {Benjamin S} and Rafael Kramann",
note = "{\textcopyright} 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = nov,
doi = "10.1038/s41588-022-01202-z",
language = "English",
volume = "54",
pages = "1690--1701",
journal = "NAT GENET",
issn = "1061-4036",
publisher = "NATURE PUBLISHING GROUP",
number = "11",

}

RIS

TY - JOUR

T1 - Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease

AU - Xu, Yaoxian

AU - Kuppe, Christoph

AU - Perales-Patón, Javier

AU - Hayat, Sikander

AU - Kranz, Jennifer

AU - Abdallah, Ali T

AU - Nagai, James

AU - Li, Zhijian

AU - Peisker, Fabian

AU - Saritas, Turgay

AU - Halder, Maurice

AU - Menzel, Sylvia

AU - Hoeft, Konrad

AU - Kenter, Annegien

AU - Kim, Hyojin

AU - van Roeyen, Claudia R C

AU - Lehrke, Michael

AU - Moellmann, Julia

AU - Speer, Thimoteus

AU - Buhl, Eva M

AU - Hoogenboezem, Remco

AU - Boor, Peter

AU - Jansen, Jitske

AU - Knopp, Cordula

AU - Kurth, Ingo

AU - Smeets, Bart

AU - Bindels, Eric

AU - Reinders, Marlies E J

AU - Baan, Carla

AU - Gribnau, Joost

AU - Hoorn, Ewout J

AU - Steffens, Joachim

AU - Huber, Tobias B

AU - Costa, Ivan

AU - Floege, Jürgen

AU - Schneider, Rebekka K

AU - Saez-Rodriguez, Julio

AU - Freedman, Benjamin S

AU - Kramann, Rafael

N1 - © 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

PY - 2022/11

Y1 - 2022/11

N2 - Adult kidney organoids have been described as strictly tubular epithelia 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+ cell-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 shows similarities in upregulation of disease-driving genes. Furthermore, in a proof of concept, we demonstrate that tolvaptan, the only approved drug for ADPKD, has a significant effect on cyst size in tubuloids but no effect on a pluripotent stem cell-derived model. Thus, tubuloids are derived from a tubular epithelial subpopulation and represent an advanced system for ADPKD disease modeling.

AB - Adult kidney organoids have been described as strictly tubular epithelia 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+ cell-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 shows similarities in upregulation of disease-driving genes. Furthermore, in a proof of concept, we demonstrate that tolvaptan, the only approved drug for ADPKD, has a significant effect on cyst size in tubuloids but no effect on a pluripotent stem cell-derived model. Thus, tubuloids are derived from a tubular epithelial subpopulation and represent an advanced system for ADPKD disease modeling.

KW - Adult

KW - Humans

KW - Polycystic Kidney, Autosomal Dominant/genetics

KW - TRPP Cation Channels/genetics

KW - Organoids

KW - Kidney

KW - Cysts

KW - CD24 Antigen/genetics

U2 - 10.1038/s41588-022-01202-z

DO - 10.1038/s41588-022-01202-z

M3 - SCORING: Journal article

C2 - 36303074

VL - 54

SP - 1690

EP - 1701

JO - NAT GENET

JF - NAT GENET

SN - 1061-4036

IS - 11

ER -