Gruffi: an algorithm for computational removal of stressed cells from brain organoid transcriptomic datasets.

ABSTRACT: Organoids enable in vitro modeling of complex developmental processes and disease pathologies. Like most 3D cultures, organoids lack sufficient oxygen supply and therefore experience cellular stress. These negative effects are particularly prominent in complex models, such as brain organoids, and can affect lineage commitment. Here, we analyze brain organoid and fetal single-cell RNA sequencing (scRNAseq) data from published and new datasets, totaling about 190,000 cells. We identify a unique stress signature in the data from all organoid samples, but not in fetal samples. We demonstrate that cell stress is limited to a defined subpopulation of cells that is unique to organoids and does not affect neuronal specification or maturation. We have developed a computational algorithm, Gruffi, wh

SUBMITTER: Vertesy A 

PROVIDER: S-EPMC9433936 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature