A comparative transcriptomic framework across kidney organoid, assembloid, and transplantation models

A recent study explores the use of kidney organoids, assembloids, and transplantation models to recapitulate human renal development. These models have proven valuable for disease modeling, nephrotoxicity screening, and therapeutic development. However, the field now encompasses various protocols with unique cellular compositions and maturation states, making systematic comparison and model selection challenging.

To address this issue, researchers integrated single-cell and single-nucleus transcriptomes from 11 studies. These studies covered kidney organoids, assembloids, and transplantation models, both in vitro and following transplantation. The research was then benchmarked against fetal and adult kidney references.

The study reveals that transcriptional maturation toward adult kidney identity is compartment-specific and does not correlate with protocol complexity. Assembloid protocols exhibit the most adult-like podocyte and distal nephron signatures among the three models. Moreover, transplantation is associated with enhanced tubular oxidative metabolic features.

Interestingly, only protocols incorporating ureteric progenitors can successfully generate collecting-duct lineages. Furthermore, no protocol achieves mature adult proximal tubule identity. When annotating against either fetal or adult kidney reference alone, the results often lead to misassignment. This is because early fetal nephron epithelium transcriptionally resembles injury-dedifferentiated adult proximal tubule cells.

One notable finding is that both assembloid and transplantation models share elevated expression of mechanosensing pathways, independent of vascularization. In conclusion, the findings of this study provide a valuable framework for selecting kidney organoid models for various research purposes.