Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis

Takasato, Minoru, Er, Pei X., Chiu, Han S., Maier, Barbara, Baillie, Gregory J., Ferguson, Charles, Parton, Robert G., Wolvetang, Ernst J., Roost, Matthias S., de Sousa Lopes, Susana M. Chuva and Little, Melissa H. (2015) Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature, 526 7574: 564-568. doi:10.1038/nature15695

Author Takasato, Minoru
Er, Pei X.
Chiu, Han S.
Maier, Barbara
Baillie, Gregory J.
Ferguson, Charles
Parton, Robert G.
Wolvetang, Ernst J.
Roost, Matthias S.
de Sousa Lopes, Susana M. Chuva
Little, Melissa H.
Title Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis
Journal name Nature   Check publisher's open access policy
ISSN 1476-4687
Publication date 2015-10-22
Year available 2015
Sub-type Letter to editor, brief commentary or brief communication
DOI 10.1038/nature15695
Open Access Status Not Open Access
Volume 526
Issue 7574
Start page 564
End page 568
Total pages 5
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1000 General
Abstract The human kidney contains up to 2 million epithelial nephrons responsible for blood filtration. Regenerating the kidney requires the induction of the more than 20 distinct cell types required for excretion and the regulation of pH, and electrolyte and fluid balance. We have previously described the simultaneous induction of progenitors for both collecting duct and nephrons via the directed differentiation of human pluripotent stem cells. Paradoxically, although both are of intermediate mesoderm in origin, collecting duct and nephrons have distinct temporospatial origins. Here we identify the developmental mechanism regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors. Using this knowledge, we have generated kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells. Within these organoids, individual nephrons segment into distal and proximal tubules, early loops of Henle, and glomeruli containing podocytes elaborating foot processes and undergoing vascularization. When transcription profiles of kidney organoids were compared to human fetal tissues, they showed highest congruence with first trimester human kidney. Furthermore, the proximal tubules endocytose dextran and differentially apoptose in response to cisplatin, a nephrotoxicant. Such kidney organoids represent powerful models of the human organ for future applications, including nephrotoxicity screening, disease modelling and as a source of cells for therapy.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP1041277
Institutional Status UQ

Document type: Journal Article
Sub-type: Letter to editor, brief commentary or brief communication
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
Australian Institute for Bioengineering and Nanotechnology Publications
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Citation counts: TR Web of Science Citation Count  Cited 167 times in Thomson Reuters Web of Science Article | Citations
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