IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33623-z.html
   My bibliography  Save this article

Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids

Author

Listed:
  • Jessica M. Vanslambrouck

    (Murdoch Children’s Research Institute
    The University of Melbourne)

  • Sean B. Wilson

    (Murdoch Children’s Research Institute
    The University of Melbourne)

  • Ker Sin Tan

    (Murdoch Children’s Research Institute)

  • Ella Groenewegen

    (Murdoch Children’s Research Institute)

  • Rajeev Rudraraju

    (The University of Melbourne)

  • Jessica Neil

    (The University of Melbourne)

  • Kynan T. Lawlor

    (Murdoch Children’s Research Institute
    The University of Melbourne)

  • Sophia Mah

    (Murdoch Children’s Research Institute)

  • Michelle Scurr

    (Murdoch Children’s Research Institute)

  • Sara E. Howden

    (Murdoch Children’s Research Institute
    The University of Melbourne)

  • Kanta Subbarao

    (The University of Melbourne)

  • Melissa H. Little

    (Murdoch Children’s Research Institute
    The University of Melbourne
    The University of Melbourne)

Abstract

While pluripotent stem cell-derived kidney organoids are now being used to model renal disease, the proximal nephron remains immature with limited evidence for key functional solute channels. This may reflect early mispatterning of the nephrogenic mesenchyme and/or insufficient maturation. Here we show that enhanced specification to metanephric nephron progenitors results in elongated and radially aligned proximalised nephrons with distinct S1 - S3 proximal tubule cell types. Such PT-enhanced organoids possess improved albumin and organic cation uptake, appropriate KIM-1 upregulation in response to cisplatin, and improved expression of SARS-CoV-2 entry factors resulting in increased viral replication. The striking proximo-distal orientation of nephrons resulted from localized WNT antagonism originating from the organoid stromal core. PT-enhanced organoids represent an improved model to study inherited and acquired proximal tubular disease as well as drug and viral responses.

Suggested Citation

  • Jessica M. Vanslambrouck & Sean B. Wilson & Ker Sin Tan & Ella Groenewegen & Rajeev Rudraraju & Jessica Neil & Kynan T. Lawlor & Sophia Mah & Michelle Scurr & Sara E. Howden & Kanta Subbarao & Melissa, 2022. "Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33623-z
    DOI: 10.1038/s41467-022-33623-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33623-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33623-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Silvia Velasco & Amanda J. Kedaigle & Sean K. Simmons & Allison Nash & Marina Rocha & Giorgia Quadrato & Bruna Paulsen & Lan Nguyen & Xian Adiconis & Aviv Regev & Joshua Z. Levin & Paola Arlotta, 2019. "Individual brain organoids reproducibly form cell diversity of the human cerebral cortex," Nature, Nature, vol. 570(7762), pages 523-527, June.
    2. Benjamin S. Freedman & Craig R. Brooks & Albert Q. Lam & Hongxia Fu & Ryuji Morizane & Vishesh Agrawal & Abdelaziz F. Saad & Michelle K. Li & Michael R. Hughes & Ryan Vander Werff & Derek T. Peters & , 2015. "Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids," Nature Communications, Nature, vol. 6(1), pages 1-13, December.
    3. Sree Deepthi Muthukrishnan & Xuehui Yang & Robert Friesel & Leif Oxburgh, 2015. "Concurrent BMP7 and FGF9 signalling governs AP-1 function to promote self-renewal of nephron progenitor cells," Nature Communications, Nature, vol. 6(1), pages 1-13, December.
    4. Shunsuke Tanigawa & Etsuko Tanaka & Koichiro Miike & Tomoko Ohmori & Daisuke Inoue & Chen-Leng Cai & Atsuhiro Taguchi & Akio Kobayashi & Ryuichi Nishinakamura, 2022. "Generation of the organotypic kidney structure by integrating pluripotent stem cell-derived renal stroma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Minoru Takasato & Pei X. Er & Han S. Chiu & Barbara Maier & Gregory J. Baillie & Charles Ferguson & Robert G. Parton & Ernst J. Wolvetang & Matthias S. Roost & Susana M. Chuva de Sousa Lopes & Melissa, 2015. "Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis," Nature, Nature, vol. 526(7574), pages 564-568, October.
    6. Shin-Ichi Mae & Akemi Shono & Fumihiko Shiota & Tetsuhiko Yasuno & Masatoshi Kajiwara & Nanaka Gotoda-Nishimura & Sayaka Arai & Aiko Sato-Otubo & Taro Toyoda & Kazutoshi Takahashi & Naoki Nakayama & C, 2013. "Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells," Nature Communications, Nature, vol. 4(1), pages 1-11, June.
    7. Peng Qiu, 2020. "Embracing the dropouts in single-cell RNA-seq analysis," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    8. Ayshwarya Subramanian & Eriene-Heidi Sidhom & Maheswarareddy Emani & Katherine Vernon & Nareh Sahakian & Yiming Zhou & Maria Kost-Alimova & Michal Slyper & Julia Waldman & Danielle Dionne & Lan T. Ngu, 2019. "Single cell census of human kidney organoids shows reproducibility and diminished off-target cells after transplantation," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    9. Charles R. Harris & K. Jarrod Millman & Stéfan J. Walt & Ralf Gommers & Pauli Virtanen & David Cournapeau & Eric Wieser & Julian Taylor & Sebastian Berg & Nathaniel J. Smith & Robert Kern & Matti Picu, 2020. "Array programming with NumPy," Nature, Nature, vol. 585(7825), pages 357-362, September.
    10. Lei Han & Xiaoyu Wei & Chuanyu Liu & Giacomo Volpe & Zhenkun Zhuang & Xuanxuan Zou & Zhifeng Wang & Taotao Pan & Yue Yuan & Xiao Zhang & Peng Fan & Pengcheng Guo & Yiwei Lai & Ying Lei & Xingyuan Liu , 2022. "Cell transcriptomic atlas of the non-human primate Macaca fascicularis," Nature, Nature, vol. 604(7907), pages 723-731, April.
    11. Madeline A. Lancaster & Magdalena Renner & Carol-Anne Martin & Daniel Wenzel & Louise S. Bicknell & Matthew E. Hurles & Tessa Homfray & Josef M. Penninger & Andrew P. Jackson & Juergen A. Knoblich, 2013. "Cerebral organoids model human brain development and microcephaly," Nature, Nature, vol. 501(7467), pages 373-379, September.
    12. Lorna J. Hale & Sara E. Howden & Belinda Phipson & Andrew Lonsdale & Pei X. Er & Irene Ghobrial & Salman Hosawi & Sean Wilson & Kynan T. Lawlor & Shahnaz Khan & Alicia Oshlack & Catherine Quinlan & Ra, 2018. "3D organoid-derived human glomeruli for personalised podocyte disease modelling and drug screening," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Moritz Lassé & Jamal El Saghir & Celine C. Berthier & Sean Eddy & Matthew Fischer & Sandra D. Laufer & Dominik Kylies & Arvid Hutzfeldt & Léna Lydie Bonin & Bernhard Dumoulin & Rajasree Menon & Virgin, 2023. "An integrated organoid omics map extends modeling potential of kidney disease," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Anand Ramani & Giovanni Pasquini & Niklas J. Gerkau & Vaibhav Jadhav & Omkar Suhas Vinchure & Nazlican Altinisik & Hannes Windoffer & Sarah Muller & Ina Rothenaigner & Sean Lin & Aruljothi Mariappan &, 2024. "Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion and drug screening," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Elaine T. Lim & Yingleong Chan & Pepper Dawes & Xiaoge Guo & Serkan Erdin & Derek J. C. Tai & Songlei Liu & Julia M. Reichert & Mannix J. Burns & Ying Kai Chan & Jessica J. Chiang & Katharina Meyer & , 2022. "Orgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Yueqi Wang & Simone Chiola & Guang Yang & Chad Russell & Celeste J. Armstrong & Yuanyuan Wu & Jay Spampanato & Paisley Tarboton & H. M. Arif Ullah & Nicolas U. Edgar & Amelia N. Chang & David A. Harmi, 2022. "Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes," Nature Communications, Nature, vol. 13(1), pages 1-25, December.
    5. Betz, Ulrich A.K. & Arora, Loukik & Assal, Reem A. & Azevedo, Hatylas & Baldwin, Jeremy & Becker, Michael S. & Bostock, Stefan & Cheng, Vinton & Egle, Tobias & Ferrari, Nicola & Schneider-Futschik, El, 2023. "Game changers in science and technology - now and beyond," Technological Forecasting and Social Change, Elsevier, vol. 193(C).
    6. Rebecca Sebastian & Kang Jin & Narciso Pavon & Ruby Bansal & Andrew Potter & Yoonjae Song & Juliana Babu & Rafael Gabriel & Yubing Sun & Bruce Aronow & ChangHui Pak, 2023. "Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Maisumu Gulimiheranmu & Shuang Li & Junmei Zhou, 2021. "In Vitro Recapitulation of Neuropsychiatric Disorders with Pluripotent Stem Cells-Derived Brain Organoids," IJERPH, MDPI, vol. 18(23), pages 1-14, November.
    8. Sienna R. Li & Ramila E. Gulieva & Louisa Helms & Nelly M. Cruz & Thomas Vincent & Hongxia Fu & Jonathan Himmelfarb & Benjamin S. Freedman, 2022. "Glucose absorption drives cystogenesis in a human organoid-on-chip model of polycystic kidney disease," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    9. Geeraert, Joke & Rocha, Luis E.C. & Vandeviver, Christophe, 2024. "The impact of violent behavior on co-offender selection: Evidence of behavioral homophily," Journal of Criminal Justice, Elsevier, vol. 94(C).
    10. Furqan Dar & Samuel R. Cohen & Diana M. Mitrea & Aaron H. Phillips & Gergely Nagy & Wellington C. Leite & Christopher B. Stanley & Jeong-Mo Choi & Richard W. Kriwacki & Rohit V. Pappu, 2024. "Biomolecular condensates form spatially inhomogeneous network fluids," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    11. López Pérez, Mario & Mansilla Corona, Ricardo, 2022. "Ordinal synchronization and typical states in high-frequency digital markets," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 598(C).
    12. Dennis Bontempi & Leonard Nuernberg & Suraj Pai & Deepa Krishnaswamy & Vamsi Thiriveedhi & Ahmed Hosny & Raymond H. Mak & Keyvan Farahani & Ron Kikinis & Andrey Fedorov & Hugo J. W. L. Aerts, 2024. "End-to-end reproducible AI pipelines in radiology using the cloud," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    13. Pablo García-Risueño, 2025. "Historical Simulation Systematically Underestimates the Expected Shortfall," JRFM, MDPI, vol. 18(1), pages 1-12, January.
    14. Lauren L. Porter & Allen K. Kim & Swechha Rimal & Loren L. Looger & Ananya Majumdar & Brett D. Mensh & Mary R. Starich & Marie-Paule Strub, 2022. "Many dissimilar NusG protein domains switch between α-helix and β-sheet folds," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    15. Oren Amsalem & Hidehiko Inagaki & Jianing Yu & Karel Svoboda & Ran Darshan, 2024. "Sub-threshold neuronal activity and the dynamical regime of cerebral cortex," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    16. Matthew Rosenblatt & Link Tejavibulya & Rongtao Jiang & Stephanie Noble & Dustin Scheinost, 2024. "Data leakage inflates prediction performance in connectome-based machine learning models," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    17. Sayedali Shetab Boushehri & Katharina Essig & Nikolaos-Kosmas Chlis & Sylvia Herter & Marina Bacac & Fabian J. Theis & Elke Glasmacher & Carsten Marr & Fabian Schmich, 2023. "Explainable machine learning for profiling the immunological synapse and functional characterization of therapeutic antibodies," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Khaled Akkad & David He, 2023. "A dynamic mode decomposition based deep learning technique for prognostics," Journal of Intelligent Manufacturing, Springer, vol. 34(5), pages 2207-2224, June.
    19. Romain Fournier & Zoi Tsangalidou & David Reich & Pier Francesco Palamara, 2023. "Haplotype-based inference of recent effective population size in modern and ancient DNA samples," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    20. Matt C. J. Denton & Luke D. Smith & Wenhao Xu & Jodeci Pugsley & Amelia Toghill & Daniel R. Kattnig, 2024. "Magnetosensitivity of tightly bound radical pairs in cryptochrome is enabled by the quantum Zeno effect," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33623-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.