Self-organisation after embryonic kidney dissociation is driven via selective adhesion of ureteric epithelial cells.
Human pluripotent stem cells, after directed differentiationin vitro, can spontaneously generate complex tissues via self-organisation of the component cells. Self-organisation can also reform embryonic organ structure after tissue disruption. It has previously been demonstrated that dissociated embryonic kidneys can recreate component epithelial and mesenchymal relationships sufficient to allow continued kidney morphogenesis. Here, we investigate the timing and underlying mechanisms driving self-organisation after dissociation of the embryonic kidney using time-lapse imaging, high-resolution confocal analyses and mathematical modelling. Organotypic self-organisation sufficient for nephron initiation was observed within a 24 h period. This involved cell movement, with structure emerging after the clustering of ureteric epithelial cells, a process consistent with models of random cell movement with preferential cell adhesion. Ureteric epithelialisation rapidly followed the formation of ureteric cell clusters with the reformation of nephron-forming niches representing a later event. Disruption of P-cadherin interactions was seen to impair this ureteric epithelial cell clustering without affecting epithelial maturation. This understanding could facilitate improved regulation of patterning within organoids and facilitate kidney engineering approaches guided by cell-cell self-organisation.
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane 4072, Australia j.lefevre@uq.edu.au.
James G
0000-0002-5945-9575
JG
Lefevre
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane 4072, Australia.
Han S
HS
Chiu
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane 4072, Australia.|Department of Anatomy and Neuroscience, Faculty of Science, University of Melbourne, Parkville 3052, Australia.|Murdoch Children's Research Institute, Parkville, Melbourne 3052, Australia.
Alexander N
0000-0001-6008-8786
AN
Combes
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane 4072, Australia.|Murdoch Children's Research Institute, Parkville, Melbourne 3052, Australia.
Jessica M
JM
Vanslambrouck
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane 4072, Australia.|Translational Research Institute, Woolloongabba, Brisbane 4102, Australia.
Ali
A
Ju
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane 4072, Australia.
Nicholas A
0000-0003-0331-3427
NA
Hamilton
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane 4072, Australia.|Murdoch Children's Research Institute, Parkville, Melbourne 3052, Australia.|Department of Pediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville 3052, Australia.
Melissa H
0000-0003-0380-2263
MH
Little
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002449:Cell Aggregation; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D003198:Computer Simulation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D007668:Kidney / Q000196:embryology*; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis; D013997:Time Factors; D014513:Ureter / Q000166:cytology*
D015820:Cadherins
Cell adhesion; Morphogenesis; Self-organisation