Single-cell transcriptomic comparison of tubular segment maturation in advanced human in vitro kidney models

Abstract

In vitro kidney models play a crucial role in the study of renal development, (patho)physiology, drug development, and potential applications in bioartificial kidneys. Human in vitro kidney models have recently advanced significantly with the development of (induced) pluripotent stem cell ((i)PSC)-derived organoids, tissue/urine-derived tubuloids, and iPSC organoid-derived tubuloids (iPSCod tubuloids). However, challenges remain in understanding degree and diversity of differentiation and each model's benefits. Here, we compared the transcriptomic profiles of kidney tubular epithelial cell types across several advanced three-dimensional (3D) models with physiological in vivo profiles (adult and fetal). Our selected models included differentiated kidney tissue-derived tubuloids, iPSCod tubuloids, and four iPSC-derived organoid models from different protocols. Our findings highlight distinct transcriptional profiles, the presence of diverse adaptive cell states, and differences in maturation marker expression among models. This study offers insights into the characteristics of state-of-the-art kidney models and guidance for researchers choosing suitable models for their investigations.