Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function

ökcen Eraslan, Eugene Drokhlyansky, Shankara Anand, Evgenij Fiskin, Ayshwarya Subramanian, Michal Slyper, Jiali Wang, Nicholas Van Wittenberghe, John M. Rouhana, Julia Waldman, Orr Ashenberg, Monkol Lek, Danielle Dionne, Thet Su Win, Michael S. Cuoco, Olena Kuksenko, Alexander M. Tsankov, Philip A. Branton, Jamie L. Marshall, Anna Greka, Gad Getz, Ayellet V. Segrè, François Aguet, Orit Rozenblatt-Rosen, Kristin G. Ardlie, Aviv Regev

Abstract

Understanding gene function and regulation in homeostasis and disease requires knowledge of the cellular and tissue contexts in which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen tissue types from 16 donors and 25 samples, generating a cross-tissue atlas of 209,126 nuclei profiles, which we integrated across tissues, donors, and laboratory methods with a conditional variational autoencoder. Using the resulting cross-tissue atlas, we highlight shared and tissue-specific features of tissue-resident cell populations; identify cell types that might contribute to neuromuscular, metabolic, and immune components of monogenic diseases and the biological processes involved in their pathology; and determine cell types and gene modules that might underlie disease mechanisms for complex traits analyzed by genome-wide association studies.

Datasets

1. Single-nucleus cross-tissue molecular reference maps to decipher disease gene function
Metadata
Sample ID_prep
assay_ontology_term_id
cell_type_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
prep
Age_bin
Sample ID
donor_id
Sample ID short
RIN score from Frozen tissue Aliquot
Autolysis Score
tissue-individual-prep
Broad cell type
Granular cell type
Tissue composition
Cell types level 2
Cell types level 3
Broad cell type (numbers)
channel
development_stage_ontology_term_id
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
GTEX_1HSMQ_5021_SM_HD2MA_CST6466 cells
GTEX_1HSMQ_5005_SM_GKSJF_EZ5196 cells
GTEX_1HSMQ_5014_SM_GKSJI_TST4359 cells
GTEX_15CHR_5005_SM_H5JDT_TST4245 cells
GTEX_12BJ1_5007_SM_H8L6U_CST4226 cells
GTEX_13N11_5030_SM_H5JDW_TST4196 cells
GTEX_144GM_5010_SM_HD2M8_NST3961 cells
GTEX_15RIE_5015_SM_H8L6X_NST3948 cells
GTEX_1HSMQ_5014_SM_GKSJI_CST3942 cells
GTEX_15SB6_5008_SM_H8L72_CST3892 cells
GTEX_1I1GU_5006_SM_G8XQC_TST3891 cells
GTEX_13N11_5030_SM_H5JDW_NST3856 cells
GTEX_145ME_5018_SM_G8XQB_TST3851 cells
GTEX_15RIE_5015_SM_H8L6X_TST3820 cells
GTEX_13N11_5002_SM_H5JDV_CST3819 cells
GTEX_13N11_5002_SM_H5JDV_NST3786 cells
GTEX_144GM_5010_SM_HD2M8_CST3759 cells
GTEX_15RIE_5015_SM_H8L6X_CST3738 cells
GTEX_13N11_5002_SM_H5JDV_TST3699 cells
GTEX_16BQI_5013_SM_H8SUW_CST3684 cells
GTEX_1HSMQ_5011_SM_GKSJH_TST3573 cells
GTEX_16BQI_5013_SM_H8SUW_TST3545 cells
GTEX_1HSMQ_5005_SM_GKSJF_TST3542 cells
GTEX_1HSMQ_5021_SM_HD2MA_NST3497 cells
GTEX_1I1GU_5006_SM_G8XQC_NST3491 cells
GTEX_1ICG6_5003_SM_GHS9A_TST3445 cells
GTEX_1ICG6_5003_SM_GHS9A_NST3444 cells
GTEX_1I1GU_5006_SM_G8XQC_CST3434 cells
GTEX_1HSMQ_5005_SM_GKSJF_CST3397 cells
GTEX_1ICG6_5014_SM_GHS9D_TST3396 cells
GTEX_1HSMQ_5011_SM_GKSJH_NST3296 cells
GTEX_145ME_5018_SM_G8XQB_EZ3271 cells
GTEX_16BQI_5013_SM_H8SUW_NST3269 cells
GTEX_13N11_5030_SM_H5JDW_CST3003 cells
GTEX_1ICG6_5014_SM_GHS9D_CST2964 cells
GTEX_145ME_5018_SM_G8XQB_NST2794 cells
GTEX_1HSMQ_5007_SM_GKSJG_TST2711 cells
GTEX_1R9PN_5002_SM_HD2MC_NST2705 cells
GTEX_145ME_5018_SM_G8XQB_CST2589 cells
GTEX_15RIE_5021_SM_H8L6Y_NST2577 cells
GTEX_1HSMQ_5021_SM_HD2MA_EZ2577 cells
GTEX_1ICG6_5003_SM_GHS9A_CST2511 cells
GTEX_145ME_5005_SM_H8L6T_TST2497 cells
GTEX_145ME_5005_SM_H8L6T_CST2374 cells
GTEX_1HSMQ_5011_SM_GKSJH_CST2291 cells
GTEX_1ICG6_5003_SM_GHS9A_EZ2273 cells
GTEX_1HSMQ_5005_SM_GKSJF_NST2269 cells
GTEX_13N11_5030_SM_H5JDW_EZ2205 cells
GTEX_1I1GU_5006_SM_G8XQC_EZ2111 cells
GTEX_12BJ1_5007_SM_H8L6U_TST2059 cells
GTEX_144GM_5010_SM_HD2M8_TST2015 cells
GTEX_15RIE_5021_SM_H8L6Y_CST1993 cells
GTEX_15RIE_5021_SM_H8L6Y_TST1988 cells
GTEX_15SB6_5008_SM_H8L72_TST1862 cells
GTEX_1R9PN_5002_SM_HD2MC_CST1777 cells
GTEX_15CHR_5005_SM_H5JDT_CST1725 cells
GTEX_1HSMQ_5011_SM_GKSJH_EZ1714 cells
GTEX_15SB6_5008_SM_H8L72_NST1674 cells
GTEX_15CHR_5005_SM_H5JDT_NST1650 cells
GTEX_1HSMQ_5007_SM_GKSJG_NST1628 cells
GTEX_1HSMQ_5014_SM_GKSJI_NST1607 cells
GTEX_1ICG6_5014_SM_GHS9D_NST1561 cells
GTEX_13N11_5002_SM_H5JDV_EZ1530 cells
GTEX_1R9PN_5002_SM_HD2MC_TST1507 cells
GTEX_1HSMQ_5021_SM_HD2MA_TST1435 cells
GTEX_1ICG6_5014_SM_GHS9D_EZ1363 cells
GTEX_145ME_5005_SM_H8L6T_NST1211 cells
GTEX_144GM_5010_SM_HD2M8_EZ1179 cells
GTEX_16BQI_5013_SM_H8SUW_EZ1010 cells
GTEX_15SB6_5008_SM_H8L72_EZ964 cells
GTEX_15RIE_5021_SM_H8L6Y_EZ940 cells
GTEX_1CAMS_5015_SM_HPJ3C_CST892 cells
GTEX_1MCC2_5013_SM_HPJ3D_NST888 cells
GTEX_1CAMS_5015_SM_HPJ3C_TST713 cells
GTEX_1HSMQ_5007_SM_GKSJG_CST622 cells
GTEX_1CAMS_5015_SM_HPJ3C_NST574 cells
GTEX_15RIE_5015_SM_H8L6X_EZ561 cells
GTEX_15CHR_5014_SM_H5JDU_TST545 cells
GTEX_15CHR_5014_SM_H5JDU_NST493 cells
GTEX_1HSMQ_5014_SM_GKSJI_EZ439 cells
GTEX_1MCC2_5013_SM_HPJ3D_TST292 cells
GTEX_15CHR_5014_SM_H5JDU_CST242 cells
GTEX_15CHR_5014_SM_H5JDU_EZ222 cells
GTEX_1MCC2_5013_SM_HPJ3D_CST196 cells
GTEX_15EOM_5003_SM_G64IH_EZ161 cells
GTEX_1CAMS_5015_SM_HPJ3C_EZ145 cells
GTEX_1MCC2_5013_SM_HPJ3D_EZ80 cells
GTEX_145ME_5005_SM_H8L6T_EZ78 cells
GTEX_15EOM_5003_SM_G64IH_CST74 cells
GTEX_15EOM_5003_SM_G64IH_NST74 cells
GTEX_1CAMR_5015_SM_HPJ3B_TST22 cells
GTEX_15EOM_5003_SM_G64IH_TST17 cells
GTEX_1CAMR_5015_SM_HPJ3B_CST16 cells
GTEX_1CAMR_5015_SM_HPJ3B_NST2 cells
GTEX_1R9PN_5002_SM_HD2MC_EZ1 cells
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Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function

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Source data

https://cellxgene.cziscience.com/collections/a3ffde6c-7ad2-498a-903c-d58e732f7470

Alias names

SCP1479, phs000424.v9.p2, PMID35549429, PMC9383269

Cite this study

Eraslan, G., Drokhlyansky, E., Anand, S., Fiskin, E., Subramanian, A., Slyper, M., Wang, J., Van Wittenberghe, N., Rouhana, J.M., Waldman, J. and Ashenberg, O., 2022. Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function. Science, 376(6594), p.eabl4290. https://doi.org/10.1126/science.abl4290