Tags

Type your tag names separated by a space and hit enter

Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta.
Ultrasound Obstet Gynecol. 2021 02; 57(2):248-256.UO

Abstract

OBJECTIVES

To examine the characteristics and distribution of possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target cells in the human trophectoderm (TE) and placenta.

METHODS

Bioinformatics analysis was performed based on published single-cell transcriptomic datasets of early TE and first- and second-trimester human placentae. We conducted the transcriptomic analysis of 4198 early TE cells, 1260 first-trimester placental cells and 189 extravillous trophoblast cells (EVTs) from 24-week placentae (EVT_24W) using the SMART-Seq2 method. In addition, to confirm the bioinformatic results, we performed immunohistochemical staining of three first-trimester, three second-trimester and three third-trimester placentae from nine women recruited prospectively to this study. We evaluated the expression of the SARS-CoV-2-related molecules angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2).

RESULTS

Via bioinformatic analysis, we identified the existence of ACE2 and TMPRSS2 expression in human TE as well as in first- and second-trimester placentae. In the human TE, 54.4% of TE1 cells, 9.0% of cytotrophoblasts (CTBs), 3.2% of EVTs and 29.5% of syncytiotrophoblasts (STBs) were ACE2-positive. In addition, 90.7% of TE1 cells, 31.5% of CTBs, 22.1% of EVTs and 70.8% of STBs were TMPRSS2-positive. In placental cells, 20.4% of CTBs, 44.1% of STBs, 3.4% of EVTs from 8-week placentae (EVT_8W) and 63% of EVT_24W were ACE2-positive, while 1.6% of CTBs, 26.5% of STBs, 1.9% of EVT_8W and 20.1% of EVT_24W were TMPRSS2-positive. Pathway analysis revealed that EVT_24W cells that were positive for both ACE2 and TMPRSS2 (ACE2 + TMPRSS2-positive) were associated with morphogenesis of branching structure, extracellular matrix interaction, oxygen binding and antioxidant activity. The ACE2 + TMPRSS2-positive TE1 cells were correlated with an increased capacity for viral invasion, epithelial-cell proliferation and cell adhesion. Expression of ACE2 and TMPRSS2 was observed on immunohistochemical staining in first-, second- and third-trimester placentae.

CONCLUSIONS

ACE2- and TMPRSS2-positive cells are present in the human TE and placenta in all three trimesters of pregnancy, which indicates the possibility that SARS-CoV-2 could spread via the placenta and cause intrauterine fetal infection. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Links

PMC Free PDF

Authors+Show Affiliations

Cui D
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China.
Liu Y
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
Jiang X
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
Ding C
Bill Lyons Informatics Centre, UCL Cancer Institute, University College London, London, UK.
Poon LC
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR.
Wang H
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
Yang H
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China. Beijing Key Laboratory of Maternal Fetal Medicine of Gestational Diabetes Mellitus, Beijing, China.

MeSH

Angiotensin-Converting Enzyme 2COVID-19FemaleFetusGene Expression ProfilingHumansInfectious Disease Transmission, VerticalPlacentaPregnancyPregnancy Complications, InfectiousProspective StudiesRNASARS-CoV-2Serine EndopeptidasesSingle-Cell AnalysisTrophoblasts

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

32851697

Citation

Cui, D, et al. "Single-cell RNA Expression Profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in Human Trophectoderm and Placenta." Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology, vol. 57, no. 2, 2021, pp. 248-256.
Cui D, Liu Y, Jiang X, et al. Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta. Ultrasound Obstet Gynecol. 2021;57(2):248-256.
Cui, D., Liu, Y., Jiang, X., Ding, C., Poon, L. C., Wang, H., & Yang, H. (2021). Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta. Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology, 57(2), 248-256. https://doi.org/10.1002/uog.22186
Cui D, et al. Single-cell RNA Expression Profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in Human Trophectoderm and Placenta. Ultrasound Obstet Gynecol. 2021;57(2):248-256. PubMed PMID: 32851697.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta. AU - Cui,D, AU - Liu,Y, AU - Jiang,X, AU - Ding,C, AU - Poon,L C, AU - Wang,H, AU - Yang,H, PY - 2020/06/13/received PY - 2020/08/08/revised PY - 2020/08/10/accepted PY - 2020/8/28/pubmed PY - 2021/2/13/medline PY - 2020/8/28/entrez KW - ACE2 KW - COVID-19 KW - SARS-CoV-2 KW - TMPRSS2 KW - placenta KW - trophectoderm SP - 248 EP - 256 JF - Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology JO - Ultrasound Obstet Gynecol VL - 57 IS - 2 N2 - OBJECTIVES: To examine the characteristics and distribution of possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target cells in the human trophectoderm (TE) and placenta. METHODS: Bioinformatics analysis was performed based on published single-cell transcriptomic datasets of early TE and first- and second-trimester human placentae. We conducted the transcriptomic analysis of 4198 early TE cells, 1260 first-trimester placental cells and 189 extravillous trophoblast cells (EVTs) from 24-week placentae (EVT_24W) using the SMART-Seq2 method. In addition, to confirm the bioinformatic results, we performed immunohistochemical staining of three first-trimester, three second-trimester and three third-trimester placentae from nine women recruited prospectively to this study. We evaluated the expression of the SARS-CoV-2-related molecules angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). RESULTS: Via bioinformatic analysis, we identified the existence of ACE2 and TMPRSS2 expression in human TE as well as in first- and second-trimester placentae. In the human TE, 54.4% of TE1 cells, 9.0% of cytotrophoblasts (CTBs), 3.2% of EVTs and 29.5% of syncytiotrophoblasts (STBs) were ACE2-positive. In addition, 90.7% of TE1 cells, 31.5% of CTBs, 22.1% of EVTs and 70.8% of STBs were TMPRSS2-positive. In placental cells, 20.4% of CTBs, 44.1% of STBs, 3.4% of EVTs from 8-week placentae (EVT_8W) and 63% of EVT_24W were ACE2-positive, while 1.6% of CTBs, 26.5% of STBs, 1.9% of EVT_8W and 20.1% of EVT_24W were TMPRSS2-positive. Pathway analysis revealed that EVT_24W cells that were positive for both ACE2 and TMPRSS2 (ACE2 + TMPRSS2-positive) were associated with morphogenesis of branching structure, extracellular matrix interaction, oxygen binding and antioxidant activity. The ACE2 + TMPRSS2-positive TE1 cells were correlated with an increased capacity for viral invasion, epithelial-cell proliferation and cell adhesion. Expression of ACE2 and TMPRSS2 was observed on immunohistochemical staining in first-, second- and third-trimester placentae. CONCLUSIONS: ACE2- and TMPRSS2-positive cells are present in the human TE and placenta in all three trimesters of pregnancy, which indicates the possibility that SARS-CoV-2 could spread via the placenta and cause intrauterine fetal infection. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. SN - 1469-0705 UR - https://www.unboundmedicine.com/medline/citation/32851697/Single_cell_RNA_expression_profiling_of_SARS_CoV_2_related_ACE2_and_TMPRSS2_in_human_trophectoderm_and_placenta_ DB - PRIME DP - Unbound Medicine ER -