Journal article

Plasticity of distal nephron epithelia from human kidney organoids enables the induction of ureteric tip and stalk

Sara E Howden, Sean B Wilson, Ella Groenewegen, Lakshi Starks, Thomas A Forbes, Ker Sin Tan, Jessica M Vanslambrouck, Emily M Holloway, Yi-Hsien Chen, Sanjay Jain, Jason R Spence, Melissa H Little

CELL STEM CELL | CELL PRESS | Published : 2021

Abstract

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"..

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Grants

Awarded by National Health and Medical Research Council, Australia


Awarded by National Institutes of Health


Awarded by Australian Research Council


Awarded by Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation


Awarded by NCI Cancer Center Support Grant


Funding Acknowledgements

We thank the Australian Genome Research Facility for access to 10x Chromium single cell library preparation and the Murdoch Children's Research Institute Translational Genomics Unit for provision of Next Generation Sequencing. M.H.L. is a Senior Principal Research Fellow of the National Health and Medical Research Council, Australia (APP1136085). This work was supported by the National Institutes of Health (UH3DK107344; U01DK107350), Australian Research Council (DP190101705), and the Dutch Kidney Foundation (RECORD KID). The primary kidney scRNA-seq was supported by grant number CZF2019-002440 from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation awarded to J.R.S. We thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, MO for the use of the Genome Engineering and Induced Pluripotent Stem Cell Center, which provided gene editing service for the Wnt9B iPSC reporter line, and Bendi Gong for technical assistance with this line. The Siteman Cancer Center is supported in part by an NCI Cancer Center Support Grant #P30 CA09184.