The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening on animal cells is a powerful tool to reveal the expression patterns of viral entry genes for different hosts. But such exploration for SARS-CoV-2 remained limited. Here, we presented the broadest pan-species single-nucleus RNA sequencing study to date, covering 11 representative species in pets (cat, dog, hamster, lizard), livestock (goat, rabbit), poultry (duck, pigeon) and wildlife (pangolin, tiger, deer), from which we investigated the co-expression of ACE2 and TMPRSS2. Notably, the proportion of SARS-CoV-2 putative target cells in cat was found considerably higher than that of other species investigated in this study, highlighting the necessity to carefully evaluate the role of cats during SARS-CoV-2 circulation. Furthermore, cross-species analysis of comparative lung cell atlas in mammals, reptiles and birds revealed core developmental programs, critical connectomes and conserved regulatory circuits among evolutionarily distant species. Additionally, we developed a user-friendly and freely accessible online platform named PANDORA for researchers to fully exploit the pan-species single cell atlas. 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 narrow down putative zoonotic reservoirs. Alternatively, our resources could also be utilized to illuminate the cellular and molecular mechanisms underlying animal tissue evolution.
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