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Howden, Wilson et al. 2020

This repository is a workflowr project showing the analysis and output relating to Howden, Wilson et al. 2020: Plasticity of distal nephron epithelia from human kidney organoids enables the induction of ureteric tip and stalk; Cell Stem Cell

Graphical Abstract

Summary

During development, distinct progenitors contribute to the nephrons versus the ureteric epithelium of the kidney. Indeed, previous human pluripotent stem-cell-derived models of kidney tissue either contain nephrons or pattern specifically to the ureteric epithelium. By re-analyzing the transcriptional distinction between distal nephron and ureteric epithelium in human fetal kidney, we show here that, while existing nephron-containing kidney organoids contain distal nephron epithelium and no ureteric epithelium, this distal nephron segment alone displays significant in vitro plasticity and can adopt a ureteric epithelial tip identity when isolated and cultured in defined conditions. “Induced” ureteric epithelium cultures can be cryopreserved, serially passaged without loss of identity, and transitioned toward a collecting duct fate. Cultures harboring loss-of-function mutations in PKHD1 also recapitulate the cystic phenotype associated with autosomal recessive polycystic kidney disease.

Authors

Sara E. Howden (lead author, contact)
Sean B. Wilson (lead author, repository owner)
Melissa H. Little (senior author, contact)
Ella Groenewegen
Lakshi Starks
Thomas A. Forbes
Ker Sin Tan
Jessica M. Vanslambrouck
Emily M. Holloway
Yi-Hsien Chen
Sanjay Jain
Jason R. Spence

Data availability

The data used in this work is available at the following locations:
GSE161255: hPSC-derived sequencing data including bulk and single cell RNA-seq
E-MTAB-9083: Human Fetal Kidney single cell RNA-seq, first published in Holloway et al. 2020

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