Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis
Top Cited Papers
- 7 October 2015
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 526 (7574), 564-568
- https://doi.org/10.1038/nature15695
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 cells1. 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.Keywords
This publication has 31 references indexed in Scilit:
- Eya1 Interacts with Six2 and Myc to Regulate Expansion of the Nephron Progenitor Pool during NephrogenesisDevelopmental Cell, 2014
- Rapid and Efficient Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubules Expressing Kidney Proximal Tubular MarkersJournal of the American Society of Nephrology, 2014
- Differentiation of Human Pluripotent Stem Cells into Nephron Progenitor Cells in a Serum and Feeder Free SystemPLOS ONE, 2014
- Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidneyNature, 2013
- Redefining the In Vivo Origin of Metanephric Nephron Progenitors Enables Generation of Complex Kidney Structures from Pluripotent Stem CellsCell Stem Cell, 2013
- Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cellsNature, 2013
- Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cellsNature Communications, 2013
- Retinoic Acid Synthesis and Signaling during Early OrganogenesisCell, 2008
- Patterning of the Avian Intermediate Mesoderm by Lateral Plate and Axial TissuesDevelopmental Biology, 2003
- The retinoic acid-inactivating enzyme CYP26 is essential for establishing an uneven distribution of retinoic acid along the anterio-posterior axis within the mouse embryoGenes & Development, 2001