Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution
Cameron S. Cowan, Magdalena Renner, Martina De Gennaro, Brigitte Gross-Scherf, David Goldblum, Yanyan Hou, Martin Munz, Tiago M. Rodrigues, Jacek Krol, Tamas Szikra, Rachel Cuttat, Annick Waldt, Panagiotis Papasaikas, Roland Diggelmann, Claudia P. Patino-Alvarez, Patricia Galliker, Stefan E. Spirig, Dinko Pavlinic, Nadine Gerber-Hollbach, Sven Schuierer, Aldin Srdanovic, Marton Balogh, Riccardo Panero, Akos Kusnyerik, Arnold Szabo, Michael B. Stadler, Selim Orgül, Simone Picelli, Pascal W. Hasler, Andreas Hierlemann, Hendrik P.N. Scholl, Guglielmo Roma, Florian Nigsch, Botond Roska
Abstract
Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable “developed” state at a rate similar to human retina development in vivo. Transcriptomes of organoid cell types converged toward the transcriptomes of adult peripheral retinal cell types. Expression of disease-associated genes was cell-type-specific in adult retina, and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas.
Datasets
1. Organoid - Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution
Metadata
cell_type_group
infomap_cluster
source
condition
dataset
sample_id
assay_ontology_term_id
donor_id
development_stage_ontology_term_id
disease_ontology_term_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sex_ontology_term_id
tissue_ontology_term_id
cell_type_ontology_term_id
author_cell_type
suspension_type
ega_sample_alias
hca_data_portal_donor_uuid
hca_data_portal_cellsuspension_uuid
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
F49-W38-B2-S1-I_CS3940 cells F49-W38-B2-S2-I_CS3469 cells F49-W30-B1-S1-I_CS2806 cells F49-W38-B2-S3-I_CS2521 cells IMR-W30-B5-S3-I_lib1_CS2422 cells IMR-W30-B4-S2-I_lib1_CS2358 cells IMR-W30-B5-S2-I_lib1_CS2318 cells IMR-W30-B4-S3-I_lib1_CS2283 cells IMR-W30-B4-S4-I_lib1_CS2038 cells F49-W30-B2-S4-I_CS1961 cells F49-W30-B2-S2-I_CS1892 cells IMR-W38-B5-S1-I_lib1_CS1819 cells F49-W30-B2-S1-I_CS1786 cells IMR-W30-B5-S1-I_lib1_CS1777 cells F49-W30-B2-S3-I_CS1726 cells IMR-W38-B4-S1-I_lib1_CS1705 cells IMR-W30-B4-S1-I_lib1_CS1660 cells IMR-W38-B4-S2-I_lib1_CS1397 cells IMR-W38-B5-S2-I_lib1_CS1353 cells IMR-W38-B4-S3-I_lib1_CS1316 cells IMR-W38-B5-S3-I_lib1_CS1310 cells NCBITaxon:960643857 cells UBERON:000096643857 cells IMR-W30-B5-S3-I_lib12422 cells IMR-W30-B4-S2-I_lib12358 cells IMR-W30-B5-S2-I_lib12318 cells IMR-W30-B4-S3-I_lib12283 cells F49-W38-B2-S1-I_lib22114 cells IMR-W30-B4-S4-I_lib12038 cells F49-W30-B2-S4-I_lib11961 cells F49-W30-B2-S2-I_lib11892 cells F49-W38-B2-S1-I_lib11826 cells F49-W38-B2-S2-I_lib11825 cells IMR-W38-B5-S1-I_lib11819 cells F49-W30-B2-S1-I_lib11786 cells IMR-W30-B5-S1-I_lib11777 cells F49-W30-B2-S3-I_lib11726 cells IMR-W38-B4-S1-I_lib11705 cells F49-W38-B2-S3-I_lib11668 cells IMR-W30-B4-S1-I_lib11660 cells F49-W38-B2-S2-I_lib21644 cells F49-W30-B1-S1-I_lib21455 cells IMR-W38-B4-S2-I_lib11397 cells IMR-W38-B5-S2-I_lib11353 cells F49-W30-B1-S1-I_lib11351 cells IMR-W38-B4-S3-I_lib11316 cells IMR-W38-B5-S3-I_lib11310 cells F49-W38-B2-S3-I_lib2853 cells 2a5f5bd4-0fe7-41bc-9134-b5865bdfe40d23756 cells c9af6a23-4beb-4ff2-b658-f0d0f3a7cb7120101 cells 9e7b6374-de32-4f59-9bdf-ae8f0caec7943940 cells 81ce7a34-3509-4ccf-80cb-bcd6d4fe798a3469 cells ba134382-52df-41a5-ae7b-80eda26b60f82806 cells 7b7efa81-35d7-42d7-8f68-7f1329b6f9f52521 cells 586d79c2-6f6a-42be-a2e0-60681e65b51a2422 cells 172f98b0-dfd6-4096-bdc7-16e12f22ebbc2358 cells f639ce84-838f-4de3-8d4a-2fa76170e0f72318 cells 3d31709f-11c3-4c1c-a88b-a6a60d8b3f462283 cells 77c5d216-adaf-495a-ac9e-a8afc338fea82038 cells 7353da6f-ef3e-4447-8cfc-5994b1a8fd611961 cells cf88b856-719b-4230-af21-0d8041dd6c7d1892 cells 49da5fd3-2847-4124-a765-a5a3e9bef7751819 cells c8b73b75-7fb4-4f00-b640-9811020d02501786 cells eccc4192-55c1-4ccc-8203-2d2391ebae6d1777 cells f9462b95-6811-424a-ab72-d1f132a6a58f1726 cells 5750068f-e6bd-4abb-864b-f3284a60f4041705 cells 2799bec6-0b4a-4842-9ed6-274bfbf070c71660 cells bc1bfbe3-892e-42d0-b70a-bb9a928db0b71397 cells 1daec61e-268f-401f-bb57-7748f0d85cdd1353 cells bd0449f0-47ee-4e07-a836-8a30918eb95b1316 cells e923ccd1-3e12-4edb-9efc-df6bfdf118d91310 cells retinal rod cell13913 cells retinal cone cell12973 cells retina horizontal cell1762 cells ON-bipolar cell1672 cells OFF-bipolar cell686 cells rod bipolar cell461 cells retinal pigment epithelial cell130 cells 2. Periphery - Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution
Metadata
cell_type_group
infomap_cluster
cell_type_label
condition
dataset
cell_type_ontology_term_id
sample_id
assay_ontology_term_id
donor_id
development_stage_ontology_term_id
disease_ontology_term_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sex_ontology_term_id
tissue_ontology_term_id
author_cell_type
suspension_type
ega_sample_alias
hca_data_portal_donor_uuid
hca_data_portal_cellsuspension_uuid
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Periphery-Left_lib52026 cells Periphery-Right_lib11987 cells Periphery-Left_lib61899 cells Periphery-Right_lib41837 cells Periphery-Left_lib11786 cells Periphery-Left_lib81647 cells Periphery-Left_lib71577 cells Periphery-Right_lib51520 cells Periphery-Right_lib71490 cells Periphery-Right_lib21479 cells Periphery-Left_lib41339 cells S-181210-00150-LPR_lib21299 cells Periphery-Right_lib61268 cells S-181210-00150-LPR_lib31118 cells Periphery-Left_lib21053 cells S-181210-00113-PRL--1-4_lib11042 cells S-181210-00153-RPR_lib21031 cells S-181210-00150-LPR_lib1988 cells S-181210-00153-RPR_lib3984 cells S-181210-00150-LPR_lib4976 cells S-181210-00153-RPR_lib1935 cells S-181210-00117-PRR--1-2_lib1825 cells S-181210-00117-PRR--1-2_lib2798 cells S-181210-00113-PRL--1-4_lib2784 cells Periphery-Left_lib3576 cells S-181210-00114-PCL--1-3_lib1415 cells S-181210-00114-PCL--1-3_lib2360 cells S-181210-00151-LPC_lib1121 cells S-181210-00151-LPC_lib4117 cells Periphery-Right_lib3111 cells S-181210-00151-LPC_lib2103 cells S-181210-00118-PCR_lib194 cells S-181210-00118-PCR_lib294 cells S-181210-00151-LPC_lib387 cells R-00646_01_LEFT_peripheral_neural_CS12945 cells R-00646_01_RIGHT_peripheral_neural_CS9692 cells R-00646_04_LEFT_peripheral_neural_CS3393 cells R-00646_04_RIGHT_peripheral_neural_CS2950 cells R-00646_03_LEFT_peripheral_neural_CS1772 cells R-00646_03_RIGHT_peripheral_neural_CS1623 cells R-00646_03_LEFT_peripheral_epithelial_CS775 cells R-00646_01_LEFT_peripheral_epithelial_CS770 cells R-00646_04_LEFT_peripheral_epithelial_CS428 cells R-00646_03_RIGHT_peripheral_epithelial_CS188 cells R-00646_01_RIGHT_peripheral_epithelial_CS187 cells HsapDv:000009134723 cells NCBITaxon:960634723 cells UBERON:000096632375 cells HS_D1_Re_P_Lf_S1_lib52026 cells HS_D1_Re_P_Rt_S1_lib11987 cells HS_D1_Re_P_Lf_S1_lib61899 cells HS_D1_Re_P_Rt_S1_lib41837 cells HS_D1_Re_P_Lf_S1_lib11786 cells HS_D1_Re_P_Lf_S1_lib81647 cells HS_D1_Re_P_Lf_S1_lib71577 cells HS_D1_Re_P_Rt_S1_lib51520 cells HS_D1_Re_P_Rt_S1_lib71490 cells HS_D1_Re_P_Rt_S1_lib21479 cells HS_D1_Re_P_Lf_S1_lib41339 cells HS_D4_Re_P_Lf_S1_lib21299 cells HS_D1_Re_P_Rt_S1_lib61268 cells HS_D4_Re_P_Lf_S1_lib31118 cells HS_D1_Re_P_Lf_S1_lib21053 cells HS_D3_Re_P_Lf_S1_lib11042 cells HS_D4_Re_P_Rt_S1_lib21031 cells HS_D4_Re_P_Lf_S1_lib1988 cells HS_D4_Re_P_Rt_S1_lib3984 cells HS_D4_Re_P_Lf_S1_lib4976 cells HS_D4_Re_P_Rt_S1_lib1935 cells HS_D3_Re_P_Rt_S1_lib1825 cells HS_D3_Re_P_Rt_S1_lib2798 cells HS_D3_Re_P_Lf_S1_lib2784 cells HS_D1_Ch_P_Lf_S1_lib1770 cells HS_D1_Re_P_Lf_S1_lib3576 cells HS_D3_Ch_P_Lf_S1_lib1415 cells HS_D3_Ch_P_Lf_S1_lib2360 cells HS_D1_Ch_P_Rt_S1_lib1187 cells HS_D4_Ch_P_Lf_S1_lib1121 cells HS_D4_Ch_P_Lf_S1_lib4117 cells HS_D1_Re_P_Rt_S1_lib3111 cells HS_D4_Ch_P_Lf_S1_lib2103 cells HS_D3_Ch_P_Rt_S1_lib194 cells HS_D3_Ch_P_Rt_S1_lib294 cells HS_D4_Ch_P_Lf_S1_lib387 cells ebf73e35-b4bc-430a-9982-c87aae7a21b623594 cells 20849833-baad-48bd-92ce-02bd1941a5516771 cells 1fbaf289-5b89-4277-b967-26db970b7e294358 cells 5a101b1b-d8dc-437a-89fd-5df520f753d012945 cells dbeea59e-e7e9-4fdb-a70f-5a6fb4a98df29692 cells 544dcdb2-a25d-4248-97cb-05477919f97b3393 cells f31a3330-2f7b-4b7f-992c-2eee031d4a3c2950 cells e4307cf1-f3aa-46ea-a0b8-5d7e5d4b5f3d1772 cells 8d1d8fed-0315-45b6-99de-3b351a65976a1623 cells 83ba61de-f433-40d8-969e-957ffce68ee1775 cells 05ef0cdb-aa74-4e03-a60a-f6541d35a03f770 cells 96d7f246-3dd6-477b-be98-bda3fe8bae19428 cells 8144c112-c8b9-4ca2-a281-98be2ca6a8fc188 cells ea536b7a-29ca-45fc-8abe-db4045cca8ef187 cells retinal rod cell13029 cells rod bipolar cell4191 cells ON-bipolar cell2130 cells OFF-bipolar cell1470 cells retinal cone cell1202 cells retina horizontal cell844 cells endothelial cell of vascular tree208 cells retinal pigment epithelial cell186 cells natural killer cell44 cells retinal ganglion cell35 cells pigment epithelium of eye2348 cells human late adulthood stage34723 cells 3. Fovea - Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution
Metadata
ega_sample_alias
sample_id
assay_ontology_term_id
donor_id
development_stage_ontology_term_id
disease_ontology_term_id
self_reported_ethnicity_ontology_term_id
organism_ontology_term_id
sex_ontology_term_id
tissue_ontology_term_id
infomap_cluster
condition
cell_type_group
cell_type_ontology_term_id
author_cell_type
suspension_type
hca_data_portal_donor_uuid
hca_data_portal_cellsuspension_uuid
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
HS_D4_Re_F_Lf_S1_lib11267 cells HS_D4_Re_F_Lf_S1_lib21153 cells HS_D1_Re_F_Rt_S1_lib21099 cells HS_D3_Re_F_Lf_S1_lib11028 cells HS_D4_Re_F_Lf_S1_lib31026 cells HS_D1_Re_F_Rt_S1_lib81024 cells HS_D3_Re_F_Lf_S1_lib21000 cells HS_D1_Re_F_Rt_S1_lib6981 cells HS_D1_Re_F_Rt_S1_lib4980 cells HS_D4_Re_F_Lf_S1_lib4973 cells HS_D1_Re_F_Rt_S1_lib7973 cells HS_D1_Re_F_Rt_S1_lib3917 cells HS_D1_Re_F_Rt_S1_lib5897 cells HS_D4_Re_F_Rt_S1_lib3883 cells HS_D4_Re_F_Rt_S1_lib2820 cells HS_D1_Re_F_Rt_S1_lib1794 cells HS_D4_Re_F_Rt_S1_lib1779 cells HS_D4_Re_F_Rt_S1_lib4753 cells HS_D3_Re_F_Rt_S1_lib2660 cells HS_D3_Re_F_Rt_S1_lib1652 cells HS_D3_Ch_F_Rt_S1_lib1272 cells HS_D3_Ch_F_Rt_S1_lib2258 cells HS_D3_Ch_F_Lf_S1_lib2157 cells HS_D3_Ch_F_Lf_S1_lib1129 cells HS_D4_Ch_F_Rt_S1_lib167 cells HS_D4_Ch_F_Lf_S1_lib363 cells HS_D4_Ch_F_Lf_S1_lib260 cells HS_D4_Ch_F_Lf_S1_lib155 cells HS_D4_Ch_F_Lf_S1_lib448 cells R-00646_01_RIGHT_foveal_neural_CS7665 cells R-00646_04_LEFT_foveal_neural_CS4419 cells R-00646_04_RIGHT_foveal_neural_CS3235 cells R-00646_03_LEFT_foveal_neural_CS2028 cells R-00646_03_RIGHT_foveal_neural_CS1312 cells R-00646_03_RIGHT_foveal_epithelial_CS530 cells R-00646_03_LEFT_foveal_epithelial_CS286 cells R-00646_04_LEFT_foveal_epithelial_CS226 cells R-00646_04_RIGHT_foveal_epithelial_CS67 cells HsapDv:000009119768 cells NCBITaxon:960619768 cells UBERON:000178619768 cells S-181210-00148-LFR_lib11267 cells S-181210-00148-LFR_lib21153 cells Fovea-Right_lib21099 cells S-181210-00111-FRL_lib11028 cells S-181210-00148-LFR_lib31026 cells Fovea-Right_lib81024 cells S-181210-00111-FRL_lib21000 cells Fovea-Right_lib6981 cells Fovea-Right_lib4980 cells S-181210-00148-LFR_lib4973 cells Fovea-Right_lib7973 cells Fovea-Right_lib3917 cells Fovea-Right_lib5897 cells S-181210-00152-RFR_lib3883 cells S-181210-00152-RFR_lib2820 cells Fovea-Right_lib1794 cells S-181210-00152-RFR_lib1779 cells S-181210-00152-RFR_lib4753 cells S-181210-00115-FRR_lib2660 cells S-181210-00115-FRR_lib1652 cells S-181210-00116-FCR_lib1272 cells S-181210-00116-FCR_lib2258 cells S-181210-00112-FCL_lib2157 cells S-181210-00112-FCL_lib1129 cells S-181210-00154-RFC67 cells S-181210-00149-LFC_lib363 cells S-181210-00149-LFC_lib260 cells S-181210-00149-LFC_lib155 cells S-181210-00149-LFC_lib448 cells 20849833-baad-48bd-92ce-02bd1941a5517947 cells ebf73e35-b4bc-430a-9982-c87aae7a21b67665 cells 1fbaf289-5b89-4277-b967-26db970b7e294156 cells 9ae24f7d-41fc-43ab-abbc-b0a364984d5e7665 cells c83e0096-47bb-4b6f-9e7e-cf7b948b7f3e4419 cells 6232212d-aee5-4934-b7c4-2aaa9e7650103235 cells 7cf4d2a2-4dd5-47b8-9ad0-87d635eadcce2028 cells 902e6bf9-b401-481a-8268-41bc8eefd2d31312 cells c8266eb2-e9f5-417c-a6fb-9e4399734242530 cells 06eebac4-e6d6-437a-a121-bcaf671ce264286 cells a41f6faa-6415-4add-8bf0-a86e0c9d4b2c226 cells 1af9abb9-4934-493b-b8ee-5f77763624b267 cells retinal ganglion cell6086 cells OFF-bipolar cell2456 cells retinal rod cell1894 cells retinal cone cell1375 cells retina horizontal cell1037 cells rod bipolar cell1016 cells endothelial cell of vascular tree368 cells natural killer cell130 cells retinal pigment epithelial cell84 cells fovea centralis19768 cells human late adulthood stage19768 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/2f4c738f-e2f3-4553-9db2-0582a38ea4dc
Alias names
EGAS00001004561, PMID32946783, PMC7505495
Cite this study
Cowan, C.S., Renner, M., De Gennaro, M., Gross-Scherf, B., Goldblum, D., Hou, Y., Munz, M., Rodrigues, T.M., Krol, J., Szikra, T. and Cuttat, R., 2020. Cell types of the human retina and its organoids at single-cell resolution. Cell, 182(6), pp.1623-1640. https://doi.org/10.1016/j.cell.2020.08.013