An integrated transcriptomic cell atlas of human neural organoids v1.0

Highlights

• An 1.7m cell integrated neural organoid atlas composed of 36 neural organoid scRNA-seq datasets using 26 different neural organoid generation protocols.
• Mapping organoid datasets to primary fetal brain identified brain regions which are currently underrepresented in neural organoid datasets.
• The HNOCA allows straightforward mapping of new organoid datasets for contextualisation of new protocols.

Overview

Neural tissues generated from human pluripotent stem cells in vitro (known as neural organoids) are becoming useful tools to study human brain development, evolution and disease. The characterization of neural organoids using single-cell genomic methods has revealed a large diversity of neural cell types with molecular signatures similar to those observed in primary human brain tissue. However, it is unclear which domains of the human nervous system are covered by existing protocols. It is also difficult to quantitatively assess variation between protocols and the specific cell states in organoids as compared to primary counterparts. Single-cell transcriptome data from primary tissue and neural organoids derived with guided or unguided approaches and under diverse conditions combined with large-scale integrative analyses make it now possible to address these challenges. Recent advances in computational methodology enable the generation of integrated atlases across many data sets. Here, we integrated 36 single-cell transcriptomics data sets spanning 26 protocols into one integrated human neural organoid cell atlas (HNOCA) totaling over 1.7 million cells. We harmonize cell type annotations by incorporating reference data sets from the developing human brain. By mapping to the developing human brain reference, we reveal which primary cell states have been generated in vitro, and which are under-represented. We further compare transcriptomic profiles of neuronal populations in organoids to their counterparts in the developing human brain. To support rapid organoid phenotyping and quantitative assessment of new protocols, we provide a programmatic interface to browse the atlas and query new data sets, and showcase the power of the atlas to annotate new query data sets and evaluate new organoid protocols. Taken together, the HNOCA will be useful to assess the fidelity of organoids, characterize perturbed and diseased states and facilitate protocol development in the future.

HNOCA

The HNOCA includes data from 36 neural organoid datasets and includes harmonised cell type annotations, as well as curated biological, and technical metadata. The datasets in the HNCOA were integrated using scPoli. The HNOCA can be used as a reference to map new datasets onto using scArches, allowing the transfer of the harmonized cell-type labels to any new dataset.

HNOCA Extended

The HNOCA extended includes 6 further datasets that have been recently published or released as a preprint. These datasets were mapped onto HNOCA with scArches, and include consensus cell type labels transferred from the HNOCA onto the mapped datasets.