A single cell transcriptome atlas of an adult cynomolgus monkey

Lei Han, Xiaoyu Wei, Chuanyu Liu, Giacomo Volpe, Zhifeng Wang, Taotao Pan, Yue Yuan, Ying Lei, Yiwei Lai, Carl Ward, Yeya Yu, Mingyue Wang, Quan Shi, Tao Wu, Liang Wu, Ya Liu, Chunqing Wang, Yuanhang Zhang, Haixi Sun, Hao Yu, Zhenkun Zhuang, Tingting Tang, Yunting Huang, Haorong Lu, Liqin Xu, Jiangshan Xu, Mengnan Cheng, Yang Liu, Chi Wai Wong, Tao Tan, Weizhi Ji, Patrick H. Maxwell, Huanming Yang, Jian Wang, Shida Zhu, Shiping Liu, Xun Xu, Yong Hou, Miguel A. Esteban and Longqi Liu. Single-cell atlas of a non-human primate reveals new pathogenic mechanisms of COVID-19. bioRxiv, 2020, DOI: https://doi.org/10.1101/2020.04.10.022103.

Mammalian tissues and organs are composed of many different cell types that can vary in abundance and cell state. Epigenetic and transcriptomic features determining this diversity are now beginning to be unravelled through the advent of single-cell profiling technologies, in particular single-cell RNA-sequencing. Although human data are accumulating, there is a substantial need for data from species phylogenetically close to human in which developmental and pathological aspects are paralleled, such as non-human primates. To aid in addressing this limitation, we have generated a high-resolution single-cell atlas of nine organs/tissues (lung, kidney, pancreas, brain, parotid, liver, thyroid, aorta and peripheral blood mononuclear cells) of a Macaca fascicularis monkey, encompassing ∼210,000 single cells. We used this dataset not only to provide fundamental information about the cellular composition of the different organs/tissues tested but also as a platform to dissect the overall expression distribution of the SARS-CoV-2 entry receptor, ACE2, and its serine protease coactivator, TMPRSS2. Our data constitute a unique resource to aid the scientific community in the fight against SARS-CoV-2 and will be instrumental for systematic comparative studies aimed at understanding physiological and pathophysiological differences between monkey and other species, in particular, human.

Figure 1 Construction of single-cell atlas across nine tissues of a Macaca fascicularis monkey. a, Schematic representation of selected monkey tissues used in this study and description of experimental pipeline for the single-cell sequencing. b, UMAP visualization of all single cells from the dataset colored by tissue/organ (left) and number of cells from each tissue passing quality control (right). c, UMAP visualization of each cell type colored according to 44 clusters in the first round of clustering. Cell type annotation is provided in the figure and is associated with a number indicative of every cluster. n = 215,334 individual nuclei/cells.

Figure 2 ACE2 and TMPRSS2 expression across 44 cell clusters in monkey.a-b, UMAP projection of ACE2 (a) and TMPRSS2 (b) expression in all single cells within our dataset. c, UMAP projection of ACE2+/TMPRSS2+ cells. d, Bubble plots showing the level of expression of TMPRSS2 and ACE2 genes and the ratio of expressing cells in the indicated cell types. The color of each bubble represents the level of expression and the size indicates the proportion of expressing cells. e, Bar plot indicating the percentage of ACE2 and TMPRSS2 expressing cells within each cell cluster.