Meta-analysis of single-cell RNA sequencing co-expression in human neural organoids reveals their high variability in recapitulating primary tissue.

Werner, Jonathan M, Gillis, Jesse (December 2024) Meta-analysis of single-cell RNA sequencing co-expression in human neural organoids reveals their high variability in recapitulating primary tissue. PLoS Biology, 22 (12). e3002912. ISSN 1544-9173

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URL: https://www.ncbi.nlm.nih.gov/pubmed/39621752

DOI: 10.1371/journal.pbio.3002912

Abstract

Human neural organoids offer an exciting opportunity for studying inaccessible human-specific brain development; however, it remains unclear how precisely organoids recapitulate fetal/primary tissue biology. We characterize field-wide replicability and biological fidelity through a meta-analysis of single-cell RNA-sequencing data for first and second trimester human primary brain (2.95 million cells, 51 data sets) and neural organoids (1.59 million cells, 173 data sets). We quantify the degree primary tissue cell type marker expression and co-expression are recapitulated in organoids across 10 different protocol types. By quantifying gene-level preservation of primary tissue co-expression, we show neural organoids lie on a spectrum ranging from virtually no signal to co-expression indistinguishable from primary tissue, demonstrating a high degree of variability in biological fidelity among organoid systems. Our preserved co-expression framework provides cell type-specific measures of fidelity applicable to diverse neural organoids, offering a powerful tool for uncovering unifying axes of variation across heterogeneous neural organoid experiments.

Item Type:	Paper
Subjects:	Investigative techniques and equipment Investigative techniques and equipment > cell culture > cancer organoids Investigative techniques and equipment > cell culture
CSHL Authors:	Werner, Jonathan Gillis, Jesse
Communities:	CSHL labs > Gillis Lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2 December 2024
Date Deposited:	19 Dec 2024 15:09
Last Modified:	19 Dec 2024 15:09
PMCID:	PMC11637388
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41762

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