Abstract
We present a strategy for increasing the anatomical realism of organoids by applying asymmetric cues to mimic spatial information that is present in natural embryonic development, and demonstrate it using mouse kidney organoids. Existing methods for making kidney organoids in mice yield developing nephrons arranged around a symmetrical collecting duct tree that has no ureter. We use transplant experiments to demonstrate plasticity in the fate choice between collecting duct and ureter, and show that an environment rich in BMP4 promotes differentiation of early collecting ducts into uroplakin-positive, unbranched, ureter-like epithelial tubules. Further, we show that application of BMP4-releasing beads in one place in an organoid can break the symmetry of the system, causing a nearby collecting duct to develop into a uroplakin-positive, broad, unbranched, ureter-like 'trunk' from one end of which true collecting duct branches radiate and induce nephron development in an arrangement similar to natural kidneys. The idea of using local symmetry-breaking cues to improve the realism of organoids may have applications to organoid systems other than the kidney.
References
Jul 14, 1998·Molecular Cell·D R HsuR M Harland
Apr 5, 2000·The Journal of Clinical Investigation·Y MiyazakiI Ichikawa
Jul 10, 1953·Science·C GROBSTEIN
Oct 7, 2004·Gene Expression Patterns : GEP·Tino D PiscioneSusan E Quaggin
Apr 20, 2007·Development·Andrea Brenner-AnantharamDoris Herzlinger
May 25, 2007·Development·Odyssé MichosRolf Zeller
Jun 27, 2008·Development·Derina SweeneyJamie A Davies
Aug 7, 2008·Cell Stem Cell·Akio KobayashiAndrew P McMahon
Dec 18, 2009·Kidney International·Mathieu Unbekandt, Jamie A Davies
May 29, 2012·Methods in Molecular Biology·Jamie A DaviesMelissa H Little
Dec 14, 2012·Nephron. Experimental Nephrology·C-Hong Chang, Jamie A Davies
Nov 10, 2013·Drug Discovery Today·Jamie Davies
Aug 5, 2014·Seminars in Cell & Developmental Biology·Tobias Bohnenpoll, Andreas Kispert
Feb 4, 2015·ELife·Nils O LindströmPeter Hohenstein
Apr 10, 2015·Current Opinion in Organ Transplantation·Melissa H Little, Minoru Takasato
Oct 8, 2015·Nature·Minoru TakasatoMelissa H Little
Oct 13, 2015·Nature Biotechnology·Ryuji MorizaneJoseph V Bonventre
Dec 1, 2015·Frontiers in Cell and Developmental Biology·Krithika HariharanKai M Schmidt-Ott
Citations
Oct 9, 2019·Journal of the Royal Society, Interface·Diana KhalipinaNicolas R Chevalier
Jan 24, 2020·Expert Opinion on Biological Therapy·Anna Julie PeiredElena Lazzeri
Jan 9, 2020·Journal of Cell Communication and Signaling·Sitong ShenYan Zhang
Jul 30, 2019·Current Opinion in Organ Transplantation·Christodoulos Xinaris
May 23, 2019·Médecine sciences : M/S·Clara SteichenThierry Hauet
Jun 9, 2020·Biochemical Society Transactions·Jamie A Davies, Fokion Glykofrydis
Mar 3, 2020·Frontiers in Medicine·Clara SteichenThierry Hauet
Sep 15, 2020·Frontiers in Cellular Neuroscience·Helga PerényiTamás Juhász
Aug 23, 2020·Journal of the American Society of Nephrology : JASN·May SallamJamie A Davies
Mar 7, 2020·Clinical Journal of the American Society of Nephrology : CJASN·Elisa Molinari, John A Sayer
Jul 16, 2019·Cell Stem Cell·Jian Hui LowYun Xia
Dec 1, 2020·Frontiers in Physiology·Ricardo Romero-GuevaraChristodoulos Xinaris
May 22, 2021·ACS Synthetic Biology·Fokion GlykofrydisJamie A Davies
Jul 30, 2021·Advanced Biology·Qasem RamadanMohammed Zourob
Jan 13, 2022·Development·Max MeuserAndreas Kispert