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Single-cell atlas of a non-human primate reveals new pathogenic mechanisms of COVID-19
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.
Longqi Liu.
Acceso Abierto
Atribución-NoComercial-SinDerivadas
10.1101/2020.04.10.022103
Stopping COVID-19 is a priority worldwide. Understanding which cell types are targeted by SARS-CoV-2 virus, whether interspecies differences exist, and how variations in cell state influence viral entry is fundamental for accelerating therapeutic and preventative approaches. In this endeavor, we profiled the transcriptome at single-cell resolution of nine tissues from a Macaca fascicularis monkey. The distribution of SARS-CoV-2 facilitators, ACE2 and TMRPSS2, in different cell subtypes showed substantial heterogeneity across lung, kidney, thyroid and liver. Co-expression analysis identified immunomodulatory proteins such as IDO2 and ANPEP as potential SARS-CoV-2 targets responsible for immune cell exhaustion. Furthermore, single-cell chromatin accessibility analysis of the kidney unveiled a plausible link between IL6-mediated innate immune responses aiming to protect tissue and enhanced ACE2 expression that could promote viral entry. Our work constitutes a unique resource for understanding SARS-CoV-2 pathophysiology in two phylogenetically close species, which might guide in the development of effective treatments in humans. Bullet pointsO_LIWe used a single-cell transcriptome atlas of 9 monkey tissues to study COVID-19. C_LIO_LIACE2+TMPRSS2+ epithelial cells of lung, kidney and liver are targets for SARS-CoV-2. C_LIO_LIACE2 correlation analysis shows IDO2 and ANPEP as potential therapeutic opportunities. C_LIO_LIWe unveil a link between IL6, STAT transcription factors and boosted SARS-CoV-2 entry. C_LI
www.biorxiv.org
2020
Artículo
https://www.biorxiv.org/content/10.1101/2020.04.10.022103v2.full.pdf
Inglés
VIRUS RESPIRATORIOS
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