Deciphering brain organoids heterogeneity by identifying key quality determinants
Brain organoids derived from human pluripotent stem cells (hPSCs) hold immense potential for modeling neurodevelopmental processes and disorders. However, their experimental variability and undefined organoid selection criteria for analysis hinder reproducibility. As part of the Bavarian ForInter consortium, we generated 72 brain organoids from distinct hPSC lines. We conducted a comprehensive analysis of their morphological and cellular characteristics at an early stage of their development. In our assessment, the Feret diameter emerged as a reliable, single parameter that characterizes brain organoid quality. Transcriptomic analysis further confirmed the reliability of this marker and identified a negative impact of mesenchymal cells on the abundance of organoid formation. High-quality organoids consistently displayed a lower mesenchymal cell presence. These findings offer a framework for enhancing brain organoid standardization and reproducibility, underscoring the need for morphological quality controls and the consideration of mesenchymal cell influence on organoid-based modeling.
Citation
@misc{kachkin2025,
author = {Kachkin, Daniil and Zagha, Naime and Boerstler, Tom and
Furlanetto, Federica and Nayebzade, Negar and Zappia, Luke and
Boisvert, Michelle and Farrell, Michaela and Ploetz, Sonja and
Regensburger, Martin and Günther, Claudia and Winkler, Juergen and
Gupta, Pooja and Theis, Fabian and Karow, Marisa and Falk, Sven and
Winner, Beate and Krach, Florian},
title = {Deciphering Brain Organoids Heterogeneity by Identifying Key
Quality Determinants},
date = {2025-01-13},
url = {https://doi.org/10.1101/2025.01.13.632763},
doi = {10.1101/2025.01.13.632763},
langid = {en},
abstract = {Brain organoids derived from human pluripotent stem cells
(hPSCs) hold immense potential for modeling neurodevelopmental
processes and disorders. However, their experimental variability and
undefined organoid selection criteria for analysis hinder
reproducibility. As part of the Bavarian ForInter consortium, we
generated 72 brain organoids from distinct hPSC lines. We conducted
a comprehensive analysis of their morphological and cellular
characteristics at an early stage of their development. In our
assessment, the Feret diameter emerged as a reliable, single
parameter that characterizes brain organoid quality. Transcriptomic
analysis further confirmed the reliability of this marker and
identified a negative impact of mesenchymal cells on the abundance
of organoid formation. High-quality organoids consistently displayed
a lower mesenchymal cell presence. These findings offer a framework
for enhancing brain organoid standardization and reproducibility,
underscoring the need for morphological quality controls and the
consideration of mesenchymal cell influence on organoid-based
modeling.}
}