ArticleScience advances2025
BrainSTEM: A single-cell multiresolution fetal brain atlas reveals transcriptomic fidelity of human midbrain cultures.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- TFAM Dependent Mitochondrial Fitness Limits CD8bioRxiv : the preprint server for biology · 2026Article
- Single-cell multi-omic atlas and morphogen screening informs midbrain and hindbrain organoid engineering.Nature neuroscience · 2026Article
- From the brain cell atlas to precision neurology: a review of the application of AI-driven multi-omics in brain science.GigaScience · 2026Review
- A single-cell transcriptomic atlas of the periventricular proliferative zone in the late gestation fetal brain in the pigtail macaque.Frontiers in neuroscience · 2026Article
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Authors and funding
6 authors.
Funding
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Abstract
Protocols for deriving midbrain dopaminergic (mDA) neurons for Parkinson's disease (PD) modeling and therapy remain incompletely benchmarked against in vivo references. To establish transcriptomic standards, we generated an integrated human fetal whole-brain atlas and a midbrain subatlas. Whole-brain analysis revealed strong region-specific signatures, underscoring the need for global mapping before refined midbrain annotation. We implemented this two-tier strategy, BrainSTEM (Brain Single-cell Two tiEr Mapping), to systematically reassess published single-cell datasets of human midbrain culture models. BrainSTEM confirmed the presence of bona fide midbrain cell types ("on-target"), but also revealed substantial populations aligning with nonmidbrain regions ("off-target"), inflating reported mDA yields across protocols. This unbiased framework enables rigorous evaluation of differentiation outcomes, clarifies current limitations of midbrain-directed models, and provides a foundation for refining protocols toward more faithful in vitro systems for PD research and regenerative applications.
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