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

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 and Melissa H. Little ()
Additional contact information
Jessica M. Vanslambrouck: Murdoch Children’s Research Institute
Sean B. Wilson: Murdoch Children’s Research Institute
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
Sophia Mah: Murdoch Children’s Research Institute
Michelle Scurr: Murdoch Children’s Research Institute
Sara E. Howden: Murdoch Children’s Research Institute
Kanta Subbarao: The University of Melbourne
Melissa H. Little: Murdoch Children’s Research Institute

Nature Communications, 2022, vol. 13, issue 1, 1-23

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33623-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33623-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33623-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().