![]() Previous studies suggested that animal tissues show high heterogeneity in terms of cellular composition and gene expression profiles, and ACE2 is only expressed in a small proportion of specific cell populations 27, thus revealing the potential application of single-cell analysis in investigating SARS-CoV-2 tropism. Single-cell sequencing has been applied to construct the single-cell atlas for a wide variety of species 20, 21, 22, 23, 24, 25, 26. Regarding the high biosafety level required for the operation of highly pathogenic live viruses such as SARS-CoV-2, experiments involving cellular or animal models are mostly restricted to a small number of qualified laboratories, which hinders the large-scale investigation for the preferential tissues and hosts for these pathogens. Because of the diverse types of receptors and potential hosts of different viruses, understanding the tissue tropism and host range of a novel virus remains challenging. However, the precise intermediate animals involved in the bat-to-human transmission of SARS-CoV-2 remain controversial and require continuous investigation.Īngiotensin-converting enzyme 2 (ACE2) has been recognized as the receptor for the spike protein of SARS-CoV, SARS-CoV-2, and HCOV-NL63 12, 18, 19. It is also reported that SARS-CoV-2 was capable of infecting cats, dogs, etc. Another mammalian animal, pangolins, has also been suggested as a potential host for SARS-CoV-2 13, 14, 15. Currently, SARS-CoV-2 shares highest sequence similarity with a bat β-CoVs (BatCoV-RaTG13) 12, indicating a probable bat origin. These six CoVs all originate from bats or rodents 6, 7, 8, 9, 10, 11. These include four epidemic CoVs causing mild respiratory symptoms in human (i.e., HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1) and two CoVs related to animal-to-human spillover events, including SARS-CoV and Middle East respiratory syndrome CoV. Before the emergence of SARS-CoV-2 in December 2019, six coronaviruses (CoVs) are able to infect humans. Most patients infected by SARS-CoV-2 displayed symptoms of fever, dry cough, headache, dyspnea, and pneumonia 5. Infected individuals without apparent clinical symptoms may also transmit the viruses 5. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for coronavirus disease 2019 (COVID-19), which continues to threaten millions of lives worldwide 1, 2, 3, 4. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. However, such exploration for SARS-CoV-2 remains limited. Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nature Communications volume 12, Article number: 7083 ( 2021) Single cell atlas for 11 non-model mammals, reptiles and birds
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