Asymmetric BMP4 signalling improves the realism of kidney organoids.

Scientific Reports
Christopher G MillsJamie A Davies

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.

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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
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
Dec 1, 2020·Frontiers in Physiology·Ricardo Romero-GuevaraChristodoulos Xinaris
May 22, 2021·ACS Synthetic Biology·Fokion GlykofrydisJamie A Davies

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