Single cell atlas for 11 non-model mammals, reptiles and birds

Abstract

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 of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. 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. 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. 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.

Screening of cell‐virus, cell‐cell, gene‐gene crosstalk among animal kingdom at single cell resolution

“… 16 , 17 , 18 We focused our attention on these viruses because of their roles in epidemics and pandemics. We first screened the expression patterns of several SARS‐CoV‐2 entry factors and cofactors in the tissues of 27 species (alpaca, mink, chinchilla, domestic guinea pig, hedgehog, horse, red‐necked wallaby, human, 19 rhesus monkey, 20 crab‐eating macaque, 21 , 22 pig‐tailed macaque [ https://portal.brain‐map.org/ ], marmoset, 22 pig, 14 , 23 hamster, 15 mouse, 24 blind mole rat, 22 rat, 13 , 22 rabbit, 15 cat, 15 tiger, 15 civet, 25 dog, 15 pangolin, 15 goat, 15 deer, 15 sheep 22 and bat 26 ). Angiotensin‐converting enzyme 2 ( ACE2 ) and the tyrosine‐protein kinase receptor UFO ( AXL ) are the cellular receptors responsible for SARS‐CoV‐2 infection, 8 , 27 while trans‐membrane serine protease ( TMPRSS2) , Neuropilin‐1 ( NRP1 ) and the high‐density lipoprotein scavenger receptor B type 1 ( SCARB1 ) are cofactors promoting the ACE2‐dependent entry of SARS‐CoV‐2.…”

“…Besides coronaviruses, we also screened for the receptor distribution of other viruses causing respiratory infection. Here, we selected 27 viral receptors corresponding to seven viral families ( Adenoviridae, Hantaviridae, Paramyxoviridae, Parvoviridae, Picornaviridae, Pneumoviridae and Reoviridae ) and screened their expression patterns in the lungs of 18 species (human, pig, mouse, rat, hamster, cat, dog, tiger, civet, rabbit, alpaca, deer, goat, bat, pangolin, duck, 15 pigeon 15 and lizard 15 ) (Figure S1 ). RPSA , a receptor for a group of parvoviruses including adeno‐associated virus 2/3/8/9, was widely expressed by different cell types in the lung of human (Clara cells), mouse (dendritic cells, macrophages, B cells, ATII, endothelial cells, ciliated cells, etc.…”

“… 11 Identifying the host and tissue tropism is the first step towards understanding viral infection and pathogenesis, thus laying the foundation for the prevention and control of putative outbreaks in animals or humans. scRNAseq data can be utilised to explore conserved or divergent cell‐cell and gene‐gene cross‐talks among multiple species, 12 , 13 , 14 , 15 resulting in various molecular circuits important in development and diseases. In this study, we constructed the single cell atlas for 20 species and characterised the expressions of virus receptors at an unprecedented scale over 75 data sets among 44 animal species.…”

Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single cell sequencing

“…We refered to the previous methodological section for cross-species homologous gene transfer and single-cell RNA-seq data processing 70 .…”

Structural Bases of Zoonotic and Zooanthroponotic Transmission of SARS-CoV-2

“…One explanation for these results is that ACE2 of cattle, sheep, and pigs may be able to successfully bind to SARS-CoV-2, but the virus cannot be completely maintained and replicated in cells to the extent that it can be transmitted. It is also likely that pigs may not express enough ACE2 to support the viral entry, which is endorsed by the observation that there are very few ACE2-expressing target cells in pigs and goats [85]. Alternative explanations have been considered and systematically eliminated following preliminary analyses.…”