tetano
Editor, Senior Moderator
Cell Rep Med
. 2022 Nov 17;100849.
doi: 10.1016/j.xcrm.2022.100849. Online ahead of print.
Human early syncytiotrophoblasts are highly susceptible to SARS-CoV-2 infection
Degong Ruan[SUP] 1 [/SUP], Zi-Wei Ye[SUP] 2 [/SUP], Shuofeng Yuan[SUP] 2 [/SUP], Zhuoxuan Li[SUP] 3 [/SUP], Weiyu Zhang[SUP] 1 [/SUP], Chon Phin Ong[SUP] 2 [/SUP], Kaiming Tang[SUP] 2 [/SUP], Timothy Theodore Ka Ki Tam[SUP] 3 [/SUP], Jilong Guo[SUP] 3 [/SUP], Yiyi Xuan[SUP] 3 [/SUP], Yunying Huang[SUP] 3 [/SUP], Qingqing Zhang[SUP] 4 [/SUP], Cheuk-Lun Lee[SUP] 4 [/SUP], Liming Lu[SUP] 5 [/SUP], Philip C N Chiu[SUP] 4 [/SUP], William S B Yeung[SUP] 6 [/SUP], Fang Liu[SUP] 7 [/SUP], Dong-Yan Jin[SUP] 8 [/SUP], Pentao Liu[SUP] 9 [/SUP]
Affiliations
Abstract
Direct in vivo investigation of human placenta trophoblast's susceptibility to SARS-CoV-2 is challenging. Here we report that human trophoblast stem cells (hTSCs) and their derivatives are susceptible to SARS-CoV-2 infection, which reveals heterogeneity in hTSC cultures. Early syncytiotrophoblasts (eSTBs) generated from hTSCs have enriched transcriptomic features of peri-implantation trophoblasts, express high levels of angiotensin-converting enzyme 2 (ACE2), and are productively infected by SARS-CoV-2 and its Delta and Omicron variants to produce virions. Antiviral drugs suppress SARS-CoV-2 replication in eSTBs and antagonize the virus-induced blockage of STB maturation. Although less susceptible to SARS-CoV-2 infection, trophoblast organoids originating from hTSCs show detectable viral replication reminiscent of the uncommon placental infection. These findings implicate possible risk of COVID-19 infection in peri-implantation embryos, which may go unnoticed. Stem cell-derived human trophoblasts such as eSTBs can potentially provide unlimited amounts of normal and genome-edited cells and facilitate coronavirus research and antiviral discovery.
Keywords: EPSC; SARS-CoV-2; expanded potential stem cell; human trophoblast; trophoblast organoid.
. 2022 Nov 17;100849.
doi: 10.1016/j.xcrm.2022.100849. Online ahead of print.
Human early syncytiotrophoblasts are highly susceptible to SARS-CoV-2 infection
Degong Ruan[SUP] 1 [/SUP], Zi-Wei Ye[SUP] 2 [/SUP], Shuofeng Yuan[SUP] 2 [/SUP], Zhuoxuan Li[SUP] 3 [/SUP], Weiyu Zhang[SUP] 1 [/SUP], Chon Phin Ong[SUP] 2 [/SUP], Kaiming Tang[SUP] 2 [/SUP], Timothy Theodore Ka Ki Tam[SUP] 3 [/SUP], Jilong Guo[SUP] 3 [/SUP], Yiyi Xuan[SUP] 3 [/SUP], Yunying Huang[SUP] 3 [/SUP], Qingqing Zhang[SUP] 4 [/SUP], Cheuk-Lun Lee[SUP] 4 [/SUP], Liming Lu[SUP] 5 [/SUP], Philip C N Chiu[SUP] 4 [/SUP], William S B Yeung[SUP] 6 [/SUP], Fang Liu[SUP] 7 [/SUP], Dong-Yan Jin[SUP] 8 [/SUP], Pentao Liu[SUP] 9 [/SUP]
Affiliations
- PMID: 36495872
- DOI: 10.1016/j.xcrm.2022.100849
Abstract
Direct in vivo investigation of human placenta trophoblast's susceptibility to SARS-CoV-2 is challenging. Here we report that human trophoblast stem cells (hTSCs) and their derivatives are susceptible to SARS-CoV-2 infection, which reveals heterogeneity in hTSC cultures. Early syncytiotrophoblasts (eSTBs) generated from hTSCs have enriched transcriptomic features of peri-implantation trophoblasts, express high levels of angiotensin-converting enzyme 2 (ACE2), and are productively infected by SARS-CoV-2 and its Delta and Omicron variants to produce virions. Antiviral drugs suppress SARS-CoV-2 replication in eSTBs and antagonize the virus-induced blockage of STB maturation. Although less susceptible to SARS-CoV-2 infection, trophoblast organoids originating from hTSCs show detectable viral replication reminiscent of the uncommon placental infection. These findings implicate possible risk of COVID-19 infection in peri-implantation embryos, which may go unnoticed. Stem cell-derived human trophoblasts such as eSTBs can potentially provide unlimited amounts of normal and genome-edited cells and facilitate coronavirus research and antiviral discovery.
Keywords: EPSC; SARS-CoV-2; expanded potential stem cell; human trophoblast; trophoblast organoid.