Kidney organoids reveal pathological mechanisms in kidney cancer
2021
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
The loss of tumour suppressor WT1 is associated with Wilms tumour development, a type of kidney cancer. Thus, there is an urge to produce in vitro models that allow easy access to the investigation of disease mechanisms and therapy development studies. Here, human induced pluripotent stem cells with WT1 knockout were used to generate kidney organoids to model Wilms tumour. The results showed that the lack of WT1 during organoid development led to kidney hyperplasia with a lack of differentiation of certain kidney cells. Moreover, the lack of WT1 blocked progenitor cell maturation, recapitulating transcriptional changes associated with a subgroup of Wilms tumour patients showing ectopic myogenesis. Furthermore, it was found that mutant WT1 cells needed untransformed microenvironments to propagate. Overall, the researchers clarify the role of WT1 in kidney development and tumour suppression and demonstrate the viability of kidney organoids as a model for paediatric cancer.
The tumor suppressor WT1 drives progenitor cell progression and epithelialization to prevent Wilms tumorigenesis in human kidney organoids
Joerg Betschinger
Added on: 11-29-2021
[1] https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00389-1
