An integrated transcriptomic cell atlas of human neural organoids

Cite

He, Z., Dony, L., Fleck, J.S., Szałata, A., Li, K.X., Slišković, I., Lin, H.C., Santel, M., Atamian, A., Quadrato, G. and Sun, J., 2024. An integrated transcriptomic cell atlas of human neural organoids. Nature, 635(8039), pp.690-698.

https://doi.org/10.1038/s41586-024-08172-8

Abstract

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 cells. Mapping to developing human brain references 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.

Datasets

1. The Human Neural Organoid Atlas

Explore
Source data
Assay type differentiation
Cell line
Cell subtype
GM
State exact
Publication
Source data DOI
Sample ID
Cell type level 1
Cell type level 2
Cell type level 3 (rev2)
Cell type
Tissue region (rev2)
Cell type (ntt_rev2)
Tissue type
Subject ID
Assay
Disease
Sex
Tissue
Ethnicity
Age
Velasco, 2019 (doi: 10.1038/s41586-019-1289-x)790,295 cells
Yoon, 2019 (doi: 10.1038/s41592-018-0255-0)213,860 cells
Lancaster, 2014 (doi: 10.1038/nprot.2014.158)192,720 cells
Fiorenzano, 2021 (doi: 10.1038/s41467-021-27464-5); standard78,940 cells
Quadrato, 2017 (doi: 10.1038/protex.2017.049)65,256 cells
Jo et al., 2016 (doi: 10.1016/j.stem.2016.07.005)59,980 cells
Qian et al., 2016 (doi: 10.1016/j.cell.2016.04.032)49,275 cells
Bhaduri, 2020 (doi: 10.1038/s41586-020-1962-0); most directed45,755 cells
Bhaduri, 2020 (doi: 10.1038/s41586-020-1962-0); directed43,308 cells
Watanabe, 2017 (doi: 10.1016/j.celrep.2017.09.047)27,874 cells
Huang, 2021 (doi: 10.1016/j.stem.2021.04.006)26,693 cells
Pasca, 2015 (doi: 10.1038/nmeth.3415)20,247 cells
Miura, 2020 (doi: 10.1038/s41587-020-00763-w)19,011 cells
Pellegrini, 2020 (doi: 10.1126/science.aaz5626); hChPO15,577 cells
Trujillo, 2019 (doi: 10.1016/j.stem.2019.08.002)14,903 cells
Quadrato, 2023 (doi: no_doi)14,285 cells
Fiorenzano, 2021 (doi:10.1038/s41467-021-27464-5); silk+laminin14,130 cells
Fiorenzano, 2021 (doi: 10.1038/s41467-021-27464-5); silk14,052 cells
Andersen, 2020 (doi: 10.1016/j.cell.2020.11.017)13,217 cells
Pellegrini, 2020 (doi: 10.1126/science.aaz5626); hCO12,214 cells
Xiang, 2019 (doi: 10.1016/j.stem.2018.12.015)10,568 cells
Esk, 2020 (doi: 10.1126/science.abb5390)8,599 cells
Qian, 2020 (doi: 10.1016/j.stem.2020.02.002)6,381 cells
Birey, 2017 (doi: 10.1038/nature22330)4,506 cells
Andersen, 2020 (doi: 10.1016/j.cell.2020.11.017); without DAPT3,486 cells
Sawada, 2020 (doi: 10.1038/s41380-020-0844-z)1,441 cells
Marton, 2019 (doi: 10.1038/s41593-018-0316-9)28 cells
An integrated transcriptomic cell atlas of human neural organoids

2. HNOCA Extended: The Human Neural Organoid Atlas

Explore
Source data
Assay type differentiation
Bio-sample
Cell line
Cell subtype
GM
State exact
Treatment
Publication
Source data DOI
Sample ID
Cell type level 1
Cell type level 2
Cell type level 3 (rev2)
Cell type level 4 (rev2)
Tissue region (rev2)
Cell type (ntt_rev2)
HNOCA core
Cell type (extended)
Tissue type
Subject ID
Assay
Disease
Sex
Tissue
Ethnicity
Age
Velasco, 2019 (doi: 10.1038/s41586-019-1289-x)790,295 cells
Yoon, 2019 (doi: 10.1038/s41592-018-0255-0)213,860 cells
Lancaster, 2014 (doi: 10.1038/nprot.2014.158)192,720 cells
nan153,108 cells
Fiorenzano, 2021 (doi: 10.1038/s41467-021-27464-5); standard78,940 cells
Quadrato, 2017 (doi: 10.1038/protex.2017.049)65,256 cells
Jo et al., 2016 (doi: 10.1016/j.stem.2016.07.005)59,980 cells
Qian et al., 2016 (doi: 10.1016/j.cell.2016.04.032)49,275 cells
Bhaduri, 2020 (doi: 10.1038/s41586-020-1962-0); most directed45,755 cells
Bhaduri, 2020 (doi: 10.1038/s41586-020-1962-0); directed43,308 cells
Watanabe, 2017 (doi: 10.1016/j.celrep.2017.09.047)27,874 cells
Huang, 2021 (doi: 10.1016/j.stem.2021.04.006)26,693 cells
Pasca, 2015 (doi: 10.1038/nmeth.3415)20,247 cells
Miura, 2020 (doi: 10.1038/s41587-020-00763-w)19,011 cells
Pellegrini, 2020 (doi: 10.1126/science.aaz5626); hChPO15,577 cells
Trujillo, 2019 (doi: 10.1016/j.stem.2019.08.002)14,903 cells
Quadrato, 2023 (doi: no_doi)14,285 cells
Fiorenzano, 2021 (doi:10.1038/s41467-021-27464-5); silk+laminin14,130 cells
Fiorenzano, 2021 (doi: 10.1038/s41467-021-27464-5); silk14,052 cells
Andersen, 2020 (doi: 10.1016/j.cell.2020.11.017)13,217 cells
Pellegrini, 2020 (doi: 10.1126/science.aaz5626); hCO12,214 cells
Xiang, 2019 (doi: 10.1016/j.stem.2018.12.015)10,568 cells
Esk, 2020 (doi: 10.1126/science.abb5390)8,599 cells
Qian, 2020 (doi: 10.1016/j.stem.2020.02.002)6,381 cells
Birey, 2017 (doi: 10.1038/nature22330)4,506 cells
Andersen, 2020 (doi: 10.1016/j.cell.2020.11.017); without DAPT3,486 cells
Sawada, 2020 (doi: 10.1038/s41380-020-0844-z)1,441 cells
Marton, 2019 (doi: 10.1038/s41593-018-0316-9)28 cells
An integrated transcriptomic cell atlas of human neural organoids

3. Disease atlas

Explore
Source data
Age (days)
Sex
Disease
Subject ID
Publication
Sample ID
Is control
Assay
Batch in data
Cell type level 1
Cell type level 2
Tissue region (rev)
Tissue region (rev2)
Leiden clustering
C9S126,744 cells
C9S218,297 cells
WTS117,194 cells
WT17,184 cells
EpiC16,410 cells
8167_2wk16,062 cells
GSE146878_SC_FXS314,766 cells
8167_Tumor12,335 cells
ISOA12,329 cells
CS29A11,857 cells
GSE146878_SC_CTRL311,241 cells
CS29B10,942 cells
ISOB10,866 cells
EpiC29,241 cells
C27,916 cells
GSM4848890_PTHS-86,466 cells
S35,836 cells
hOrg190111_Org25,139 cells
S14,895 cells
GSM4848887_PTHS-54,764 cells
C14,586 cells
hOrg180105-A24,585 cells
1371214,567 cells
AD4,415 cells
Control_6M4,120 cells
8036_8wk4,064 cells
GSM5844877_EML14,055 cells
MECP2_MECP23,917 cells
GSM4848888_PTHS-63,792 cells
hOrg180905-Org13,773 cells
8165PV_2wk3,753 cells
1371203,732 cells
MECP2_WT3,681 cells
hOrg190111_Org13,665 cells
1371223,620 cells
GSM4473314_SC_CTRL23,588 cells
8167_24wk3,586 cells
GSM4848885_PTHS-33,544 cells
NDC3,530 cells
1371233,518 cells
GSM4848883_PTHS-13,492 cells
1371183,427 cells
GSM4848884_PTHS-23,368 cells
8165C_24wk3,357 cells
8165C_Tumor3,229 cells
GSM5844876_Control3,180 cells
GSM4848889_PTHS-73,066 cells
8165PV_24wk3,030 cells
GSM4848886_PTHS-42,944 cells
8036_Tumor2,928 cells
DM600_6M2,907 cells
BATCH3_2136642,888 cells
1371192,876 cells
DM1200_6M2,773 cells
1371162,755 cells
8165PV_Tumor2,735 cells
BATCH3_2136632,728 cells
1371172,713 cells
GSM4473313_SC_CTRL12,676 cells
GSM4473315_SC_FXS12,547 cells
8036_2wk2,463 cells
C32,403 cells
206287_rnacount2,337 cells
hOrg180105-A12,306 cells
8165C_2wk2,287 cells
BATCH3_2136621,982 cells
206290_rnacount1,948 cells
GSM4473316_SC_FXS21,739 cells
BATCH3_2136611,645 cells
206282_rnacount1,607 cells
206288_rnacount1,491 cells
206289_rnacount1,391 cells
206286_rnacount1,193 cells
S21,098 cells
C41,052 cells
206285_rnacount1,037 cells
206291_rnacount956 cells
206284_rnacount762 cells
206283_rnacount581 cells
Control_3b94 cells
Dchs1_391 cells
Control_3a91 cells
Dchs1_187 cells
Fat4_283 cells
Fat4_379 cells
Dchs1_277 cells
Fat4_172 cells
Control_266 cells
Control_165 cells
An integrated transcriptomic cell atlas of human neural organoids