TY - JOUR
KW - Data integration
KW - Developmental neurogenesis
KW - Neural Stem Cells
KW - Transcriptomics
AU - Zhisong He
AU - Leander Dony
AU - Jonas Simon Fleck
AU - Artur Szałata
AU - Katelyn X. Li
AU - Irena Slišković
AU - Hsiu-Chuan Lin
AU - Malgorzata Santel
AU - Alexander Atamian
AU - Giorgia Quadrato
AU - Jieran Sun
AU - Sergiu P. Pașca
AU - J. Gray Camp
AU - Fabian J. Theis
AU - Barbara Treutlein
AB - Human neural organoids, generated from pluripotent stem cells in vitro, are useful tools to study human brain development, evolution and disease. However, it is unclear which parts of the human brain are covered by existing protocols, and it has been difficult to quantitatively assess organoid variation and fidelity. Here we integrate 36 single-cell transcriptomic datasets spanning 26 protocols into one integrated human neural organoid cell atlas totalling more than 1.7 million cells1–26. Mapping to developing human brain references27–30 shows primary cell types and states that have been generated in vitro, and estimates transcriptomic similarity between primary and organoid counterparts across protocols. We provide a programmatic interface to browse the atlas and query new datasets, and showcase the power of the atlas to annotate organoid cell types and evaluate new organoid protocols. Finally, we show that the atlas can be used as a diverse control cohort to annotate and compare organoid models of neural disease, identifying genes and pathways that may underlie pathological mechanisms with the neural models. The human neural organoid cell atlas will be useful to assess organoid fidelity, characterize perturbed and diseased states and facilitate protocol development.
BT - Nature
DA - 2024-11
DO - 10.1038/s41586-024-08172-8
IS - 8039
LA - en
N2 - Human neural organoids, generated from pluripotent stem cells in vitro, are useful tools to study human brain development, evolution and disease. However, it is unclear which parts of the human brain are covered by existing protocols, and it has been difficult to quantitatively assess organoid variation and fidelity. Here we integrate 36 single-cell transcriptomic datasets spanning 26 protocols into one integrated human neural organoid cell atlas totalling more than 1.7 million cells1–26. Mapping to developing human brain references27–30 shows primary cell types and states that have been generated in vitro, and estimates transcriptomic similarity between primary and organoid counterparts across protocols. We provide a programmatic interface to browse the atlas and query new datasets, and showcase the power of the atlas to annotate organoid cell types and evaluate new organoid protocols. Finally, we show that the atlas can be used as a diverse control cohort to annotate and compare organoid models of neural disease, identifying genes and pathways that may underlie pathological mechanisms with the neural models. The human neural organoid cell atlas will be useful to assess organoid fidelity, characterize perturbed and diseased states and facilitate protocol development.
PY - 2024
SP - 690
EP - 698
T2 - Nature
TI - An integrated transcriptomic cell atlas of human neural organoids
UR - https://www.nature.com/articles/s41586-024-08172-8
VL - 635
Y2 - 2024-11-26
SN - 1476-4687
ER -