Abstract
Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell–cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.
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Data availability
All raw data produced in this study (including NHPCA and mouse neocortex data) have been deposited to the CNGB Nucleotide Sequence Archive (accession code CNP0001469). All NHPCA count matrix data are available from https://db.cngb.org/nhpca/download. We have also provided the NHPCA website (https://db.cngb.org/nhpca/), an open and interactive database for exploration. The public datasets used in this study can be accessed as described below: the HCL count matrix is available at https://figshare.com/articles/dataset/HCL_DGE_Data/7235471, the MCA count matrix is available at https://figshare.com/articles/dataset/MCA_DGE_Data/5435866 and the count matrix for the Tabula Muris dataset is available at https://figshare.com/projects/Tabula_Muris_Transcriptomic_characterization_of_20_organs_and_tissues_from_Mus_musculus_at_single_cell_resolution/27733. The Gene Expression Omnibus (GEO) accession numbers for the two human kidney datasets are GSE121862 and GSE151302. The GEO accession number for the mouse kidney data is GSE107585. The GEO accession number for the human neocortex data is GSE97942. The human heart data can be accessed at the European Nucleotide Archive (https://www.ebi.ac.uk/ena/) using accession number ERP123138. The mouse heart data can be found through accession number E-MTAB-7869 in the database of the European Bioinformatics Institute (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-7869/). Summary statistics files for each human trait were downloaded from the UK Biobank database or published studies (data links in Supplementary Table 6a). Source data are provided with this paper.
Code availability
Computer code used for processing the snRNA-seq, scRNA-seq and scATAC-seq data is available at https://github.com/single-cell-BGI/NHPCA.
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Acknowledgements
We thank W. Liu and L. Xu from the Huazhen Laboratory Animal Breeding Centre for helping in the collection of monkey tissues, D. Zhu and H. Li from the Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) for technical help, G. Guo and H. Sun from Zhejiang University for providing HCL and MCA gene expression data matrices, G. Dong and C. Liu from BGI Research, and X. Zhang, P. Li and C. Qi from the Guangzhou Institutes of Biomedicine and Health for experimental advice or providing reagents. This work was supported by the Shenzhen Basic Research Project for Excellent Young Scholars (RCYX20200714114644191), Shenzhen Key Laboratory of Single-Cell Omics (ZDSYS20190902093613831), Shenzhen Bay Laboratory (SZBL2019062801012) and Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011). In addition, L.L. was supported by the National Natural Science Foundation of China (31900466), Y. Hou was supported by the Natural Science Foundation of Guangdong Province (2018A030313379) and M.A.E. was supported by a Changbai Mountain Scholar award (419020201252), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030502), a Chinese Academy of Sciences–Japan Society for the Promotion of Science joint research project (GJHZ2093), the National Natural Science Foundation of China (92068106, U20A2015) and the Guangdong Basic and Applied Basic Research Foundation (2021B1515120075). M.L. was supported by the National Key Research and Development Program of China (2021YFC2600200).
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L.H., Y. Hou, X.X., M.A.E. and L.L. conceived the idea; Y. Hou, X.X., M.A.E. and L.L. supervised the work; L.H., Xiaoyu Wei, Y. Yuan, M.A.E. and L.L. designed the experiments; L.H., Xiaoyu Wei, G.V., Y. Yuan, X. Zhang, P.F., P.G., Xingyuan Liu, F.Y., S.S., G.L., J.A., Y. Lei, Y. Lai, M.C., C.-W. Wong, X.G., S.L. and J.M. collected tissue samples; C.L., G.V., Zhifeng Wang, Y. Yuan, X. Zhang, P.F., Q.D., Ya Liu, Y. Huang, H.L., B.W., M.C., J.X., M.W., C. Wang, Y.Z., Y. Yu, H. Zheng, Y.W. and S.X. performed the experiments. L.H., Xiaoyu Wei, G.V., Z. Zhuang, X. Zou, T.P., Y. Lai, L.W., Q. Shi, H. Yu, Yang Liu, D.X., F.H., Z. Zhu and C. Ward performed data analysis. L.H., Xiaoyu Wei, C.L., G.V., Z. Zhuang, X. Zou, Z. Wang, T.P., Y. Yang, J.L. and L.L. prepared the figures. H. Yu, Xiaofeng Wei, F.C., T.Y., W.D. and J.C. prepared the website. Zongren Wang, Z.P., C.-W.W., B.Q., A.S., J.I., L.F., Yan Liu, Z.L., Xiaolei Liu, H. Zhang, M.L., Q. Sun, P.H.M., N.B., P.M.-C., Y.G., J.M., M.U., T.T., S.L., H. Yang and J.W. provided relevant advice and reviewed the manuscript. L.H., G.V., M.A.E. and L.L. wrote the manuscript with input from all authors. All other authors contributed to the work. All authors read and approved the manuscript for submission.
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This file contains the Supplementary Note, the legends for Supplementary Figs. 1–46 and the legends for Supplementary Tables 1–6.
Supplementary Table 1
Description of all profiled monkey tissues, cell types and markers used for cluster annotation.
Supplementary Table 2
Global analysis of monkey common cell types and tissue-specific signatures.
Supplementary Table 3
Global distribution of LGR5, LGR6 and MKI67 expression in monkey tissues.
Supplementary Table 4
Species-specific genes in kidney DCTCs between monkey, human and mouse.
Supplementary Table 5
Expression of virus receptors, ACE2 and TMPRSS2 in monkey tissues.
Supplementary Table 6
Association of GWAS traits and human genetic diseases with monkey cell types.
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Han, L., Wei, X., Liu, C. et al. Cell transcriptomic atlas of the non-human primate Macaca fascicularis. Nature 604, 723–731 (2022). https://doi.org/10.1038/s41586-022-04587-3
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DOI: https://doi.org/10.1038/s41586-022-04587-3
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