Differentiated mouse kidney tubuloids as a novel in vitro model to study collecting duct physiology
Kidney tubuloids are cell models that are derived from human or mouse renal epithelial cells and show high similarities with their in vivo counterparts. Tubuloids grow polarized in 3D, allow for long-term expansion, and represent multiple segments of the nephron, as shown by their gene expression pa...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1086823/full |
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| author | C. J. A. Olde Hanhof E. Dilmen F. A. Yousef Yengej F. A. Yousef Yengej F. Latta C. M. E. Ammerlaan C. M. E. Ammerlaan J. Schreurs L. Hooijmaijers J. Jansen J. Jansen J. Jansen M. B. Rookmaaker I. Orhon M. C. Verhaar J. G. Hoenderop |
| author_facet | C. J. A. Olde Hanhof E. Dilmen F. A. Yousef Yengej F. A. Yousef Yengej F. Latta C. M. E. Ammerlaan C. M. E. Ammerlaan J. Schreurs L. Hooijmaijers J. Jansen J. Jansen J. Jansen M. B. Rookmaaker I. Orhon M. C. Verhaar J. G. Hoenderop |
| author_sort | C. J. A. Olde Hanhof |
| collection | DOAJ |
| description | Kidney tubuloids are cell models that are derived from human or mouse renal epithelial cells and show high similarities with their in vivo counterparts. Tubuloids grow polarized in 3D, allow for long-term expansion, and represent multiple segments of the nephron, as shown by their gene expression pattern. In addition, human tubuloids form tight, functional barriers and have been succesfully used for drug testing. Our knowledge of mouse tubuloids, on the other hand, is only minimal. In this study, we further characterized mouse tubuloids and differentiated them towards the collecting duct, which led to a significant upregulation of collecting duct-specific mRNAs of genes and protein expression, including the water channel AQP2 and the sodium channel ENaC. Differentiation resulted in polarized expression of collecting duct water channels AQP2 and AQP3. Also, a physiological response to desmopressin and forskolin stimulation by translocation of AQP2 to the apical membrane was demonstrated. Furthermore, amiloride-sensitive ENaC-mediated sodium uptake was shown in differentiated tubuloids using radioactive tracer sodium. This study demonstrates that mouse tubuloids can be differentiated towards the collecting duct and exhibit collecting duct-specific function. This illustrates the potential use of mouse kidney tubuloids as novel in vitro models to study (patho)physiology of kidney diseases. |
| first_indexed | 2024-04-10T20:29:14Z |
| format | Article |
| id | doaj.art-0fc2230c8cac4d188a5f1ed80d60dec5 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-10T20:29:14Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-0fc2230c8cac4d188a5f1ed80d60dec52023-01-25T07:05:25ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-01-011110.3389/fcell.2023.10868231086823Differentiated mouse kidney tubuloids as a novel in vitro model to study collecting duct physiologyC. J. A. Olde Hanhof0E. Dilmen1F. A. Yousef Yengej2F. A. Yousef Yengej3F. Latta4C. M. E. Ammerlaan5C. M. E. Ammerlaan6J. Schreurs7L. Hooijmaijers8J. Jansen9J. Jansen10J. Jansen11M. B. Rookmaaker12I. Orhon13M. C. Verhaar14J. G. Hoenderop15Department of Molecular Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Molecular Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsHubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht, NetherlandsDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Molecular Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsHubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht, NetherlandsDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Molecular Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Molecular Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Amalia Children’s Hospital, Nijmegen, NetherlandsInstitute of Experimental Medicine and Systems Biology, Medical Faculty RWTH Aachen University, Aachen, GermanyDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Molecular Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Molecular Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsKidney tubuloids are cell models that are derived from human or mouse renal epithelial cells and show high similarities with their in vivo counterparts. Tubuloids grow polarized in 3D, allow for long-term expansion, and represent multiple segments of the nephron, as shown by their gene expression pattern. In addition, human tubuloids form tight, functional barriers and have been succesfully used for drug testing. Our knowledge of mouse tubuloids, on the other hand, is only minimal. In this study, we further characterized mouse tubuloids and differentiated them towards the collecting duct, which led to a significant upregulation of collecting duct-specific mRNAs of genes and protein expression, including the water channel AQP2 and the sodium channel ENaC. Differentiation resulted in polarized expression of collecting duct water channels AQP2 and AQP3. Also, a physiological response to desmopressin and forskolin stimulation by translocation of AQP2 to the apical membrane was demonstrated. Furthermore, amiloride-sensitive ENaC-mediated sodium uptake was shown in differentiated tubuloids using radioactive tracer sodium. This study demonstrates that mouse tubuloids can be differentiated towards the collecting duct and exhibit collecting duct-specific function. This illustrates the potential use of mouse kidney tubuloids as novel in vitro models to study (patho)physiology of kidney diseases.https://www.frontiersin.org/articles/10.3389/fcell.2023.1086823/fulltubuloidorganoidepithelial sodium transportcell physiologycollecting ducttubulopathy |
| spellingShingle | C. J. A. Olde Hanhof E. Dilmen F. A. Yousef Yengej F. A. Yousef Yengej F. Latta C. M. E. Ammerlaan C. M. E. Ammerlaan J. Schreurs L. Hooijmaijers J. Jansen J. Jansen J. Jansen M. B. Rookmaaker I. Orhon M. C. Verhaar J. G. Hoenderop Differentiated mouse kidney tubuloids as a novel in vitro model to study collecting duct physiology Frontiers in Cell and Developmental Biology tubuloid organoid epithelial sodium transport cell physiology collecting duct tubulopathy |
| title | Differentiated mouse kidney tubuloids as a novel in vitro model to study collecting duct physiology |
| title_full | Differentiated mouse kidney tubuloids as a novel in vitro model to study collecting duct physiology |
| title_fullStr | Differentiated mouse kidney tubuloids as a novel in vitro model to study collecting duct physiology |
| title_full_unstemmed | Differentiated mouse kidney tubuloids as a novel in vitro model to study collecting duct physiology |
| title_short | Differentiated mouse kidney tubuloids as a novel in vitro model to study collecting duct physiology |
| title_sort | differentiated mouse kidney tubuloids as a novel in vitro model to study collecting duct physiology |
| topic | tubuloid organoid epithelial sodium transport cell physiology collecting duct tubulopathy |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1086823/full |
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