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
GM
State exact
Publication
Source data DOI
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)790295 cells
Yoon, 2019 (doi: 10.1038/s41592-018-0255-0)213860 cells
Lancaster, 2014 (doi: 10.1038/nprot.2014.158)192720 cells
Fiorenzano, 2021 (doi: 10.1038/s41467-021-27464-5); standard78940 cells
Quadrato, 2017 (doi: 10.1038/protex.2017.049)65256 cells
Jo et al., 2016 (doi: 10.1016/j.stem.2016.07.005)59980 cells
Qian et al., 2016 (doi: 10.1016/j.cell.2016.04.032)49275 cells
Bhaduri, 2020 (doi: 10.1038/s41586-020-1962-0); most directed45755 cells
Bhaduri, 2020 (doi: 10.1038/s41586-020-1962-0); directed43308 cells
Watanabe, 2017 (doi: 10.1016/j.celrep.2017.09.047)27874 cells
Huang, 2021 (doi: 10.1016/j.stem.2021.04.006)26693 cells
Pasca, 2015 (doi: 10.1038/nmeth.3415)20247 cells
Miura, 2020 (doi: 10.1038/s41587-020-00763-w)19011 cells
Pellegrini, 2020 (doi: 10.1126/science.aaz5626); hChPO15577 cells
Trujillo, 2019 (doi: 10.1016/j.stem.2019.08.002)14903 cells
Quadrato, 2023 (doi: no_doi)14285 cells
Fiorenzano, 2021 (doi:10.1038/s41467-021-27464-5); silk+laminin14130 cells
Fiorenzano, 2021 (doi: 10.1038/s41467-021-27464-5); silk14052 cells
Andersen, 2020 (doi: 10.1016/j.cell.2020.11.017)13217 cells
Pellegrini, 2020 (doi: 10.1126/science.aaz5626); hCO12214 cells
Xiang, 2019 (doi: 10.1016/j.stem.2018.12.015)10568 cells
Esk, 2020 (doi: 10.1126/science.abb5390)8599 cells
Qian, 2020 (doi: 10.1016/j.stem.2020.02.002)6381 cells
Birey, 2017 (doi: 10.1038/nature22330)4506 cells
Andersen, 2020 (doi: 10.1016/j.cell.2020.11.017); without DAPT3486 cells
Sawada, 2020 (doi: 10.1038/s41380-020-0844-z)1441 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
Cell line
GM
State exact
Treatment
Publication
Source data DOI
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)790295 cells
Yoon, 2019 (doi: 10.1038/s41592-018-0255-0)213860 cells
Lancaster, 2014 (doi: 10.1038/nprot.2014.158)192720 cells
nan153108 cells
Fiorenzano, 2021 (doi: 10.1038/s41467-021-27464-5); standard78940 cells
Quadrato, 2017 (doi: 10.1038/protex.2017.049)65256 cells
Jo et al., 2016 (doi: 10.1016/j.stem.2016.07.005)59980 cells
Qian et al., 2016 (doi: 10.1016/j.cell.2016.04.032)49275 cells
Bhaduri, 2020 (doi: 10.1038/s41586-020-1962-0); most directed45755 cells
Bhaduri, 2020 (doi: 10.1038/s41586-020-1962-0); directed43308 cells
Watanabe, 2017 (doi: 10.1016/j.celrep.2017.09.047)27874 cells
Huang, 2021 (doi: 10.1016/j.stem.2021.04.006)26693 cells
Pasca, 2015 (doi: 10.1038/nmeth.3415)20247 cells
Miura, 2020 (doi: 10.1038/s41587-020-00763-w)19011 cells
Pellegrini, 2020 (doi: 10.1126/science.aaz5626); hChPO15577 cells
Trujillo, 2019 (doi: 10.1016/j.stem.2019.08.002)14903 cells
Quadrato, 2023 (doi: no_doi)14285 cells
Fiorenzano, 2021 (doi:10.1038/s41467-021-27464-5); silk+laminin14130 cells
Fiorenzano, 2021 (doi: 10.1038/s41467-021-27464-5); silk14052 cells
Andersen, 2020 (doi: 10.1016/j.cell.2020.11.017)13217 cells
Pellegrini, 2020 (doi: 10.1126/science.aaz5626); hCO12214 cells
Xiang, 2019 (doi: 10.1016/j.stem.2018.12.015)10568 cells
Esk, 2020 (doi: 10.1126/science.abb5390)8599 cells
Qian, 2020 (doi: 10.1016/j.stem.2020.02.002)6381 cells
Birey, 2017 (doi: 10.1038/nature22330)4506 cells
Andersen, 2020 (doi: 10.1016/j.cell.2020.11.017); without DAPT3486 cells
Sawada, 2020 (doi: 10.1038/s41380-020-0844-z)1441 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
Is control
Assay
Batch in data
Cell type level 1
Cell type level 2
Tissue region (rev)
Tissue region (rev2)
Leiden clustering
C9S126744 cells
C9S218297 cells
WTS117194 cells
WT17184 cells
EpiC16410 cells
8167_2wk16062 cells
GSE146878_SC_FXS314766 cells
8167_Tumor12335 cells
ISOA12329 cells
CS29A11857 cells
GSE146878_SC_CTRL311241 cells
CS29B10942 cells
ISOB10866 cells
EpiC29241 cells
C27916 cells
GSM4848890_PTHS-86466 cells
S35836 cells
hOrg190111_Org25139 cells
S14895 cells
GSM4848887_PTHS-54764 cells
C14586 cells
hOrg180105-A24585 cells
1371214567 cells
AD4415 cells
Control_6M4120 cells
8036_8wk4064 cells
GSM5844877_EML14055 cells
MECP2_MECP23917 cells
GSM4848888_PTHS-63792 cells
hOrg180905-Org13773 cells
8165PV_2wk3753 cells
1371203732 cells
MECP2_WT3681 cells
hOrg190111_Org13665 cells
1371223620 cells
GSM4473314_SC_CTRL23588 cells
8167_24wk3586 cells
GSM4848885_PTHS-33544 cells
NDC3530 cells
1371233518 cells
GSM4848883_PTHS-13492 cells
1371183427 cells
GSM4848884_PTHS-23368 cells
8165C_24wk3357 cells
8165C_Tumor3229 cells
GSM5844876_Control3180 cells
GSM4848889_PTHS-73066 cells
8165PV_24wk3030 cells
GSM4848886_PTHS-42944 cells
8036_Tumor2928 cells
DM600_6M2907 cells
BATCH3_2136642888 cells
1371192876 cells
DM1200_6M2773 cells
1371162755 cells
8165PV_Tumor2735 cells
BATCH3_2136632728 cells
1371172713 cells
GSM4473313_SC_CTRL12676 cells
GSM4473315_SC_FXS12547 cells
8036_2wk2463 cells
C32403 cells
206287_rnacount2337 cells
hOrg180105-A12306 cells
8165C_2wk2287 cells
BATCH3_2136621982 cells
206290_rnacount1948 cells
GSM4473316_SC_FXS21739 cells
BATCH3_2136611645 cells
206282_rnacount1607 cells
206288_rnacount1491 cells
206289_rnacount1391 cells
206286_rnacount1193 cells
S21098 cells
C41052 cells
206285_rnacount1037 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