Publication Date:
2015-10-08
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takasato, Minoru -- Er, Pei X -- Chiu, Han S -- Maier, Barbara -- Baillie, Gregory J -- Ferguson, Charles -- Parton, Robert G -- Wolvetang, Ernst J -- Roost, Matthias S -- Chuva de Sousa Lopes, Susana M -- Little, Melissa H -- England -- Nature. 2015 Oct 22;526(7574):564-8. doi: 10.1038/nature15695. Epub 2015 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Murdoch Childrens Research Institute, The Royal Children's Hospital Melbourne, Parkville, Victoria 3052, Australia. ; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia. ; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Queensland 4072, Australia. ; Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands. ; Department of Paediatrics, The University of Melbourne, Parkville, Victoria 3010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26444236" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Cell Lineage
;
Coculture Techniques
;
Feeder Cells
;
Fetus/anatomy & histology/cytology/embryology
;
Fibroblasts/cytology
;
Humans
;
Induced Pluripotent Stem Cells/*cytology
;
Kidney Tubules, Collecting/cytology
;
Kidney Tubules, Proximal/cytology/embryology/physiology
;
Mesoderm/cytology
;
Mice
;
*Models, Biological
;
Nephrons/anatomy & histology/*cytology/*embryology/physiology
;
*Organogenesis
;
Organoids/*cytology/embryology
;
Tissue Culture Techniques
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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