Tissue Type(s): Placenta 

Contributed by: Yuk Ming Dennis Lo, The Chinese University of Hong Kong

Manuscript: Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells (https://www.biorxiv.org/content/10.1101/2020.04.19.049254v1

Description: This study allows one to download the data associated with this manuscript and is a subset of what may be made available by the original manuscript. 

Original Publication: Tsang, J. C. H., Vong, J. S. L., Ji, L., Poon, L. C. Y., Jiang, P., Lui, K. O., Ni, Y.-B., To, K. F., Cheng, Y. K. Y., Chiu, R. W. K., & Lo, Y. M. D. (2017). Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics. Proceedings of the National Academy of Sciences of the United States of America, 114(37), E7786–E7795.

Full dataset: The sequence data for the subjects studied in this work who had consented to data archiving have been deposited in the European Genome-Phenome Archive (EGA; https://www.ebi.ac.uk/ega/) hosted by the European Bioinformatics Institute (EBI; accession no. EGAS00001002449).

Abstract: The human placenta is a dynamic and heterogeneous organ critical in the establishment of the fetomaternal interface and the maintenance of gestational well-being. It is also the major source of cell-free fetal nucleic acids in the maternal circulation. Placental dysfunction contributes to significant complications, such as preeclampsia, a potentially lethal hypertensive disorder during pregnancy. Previous studies have identified significant changes in the expression profiles of preeclamptic placentas using whole-tissue analysis. Moreover, studies have shown increased levels of targeted RNA transcripts, overall and placental contributions in maternal cell-free nucleic acids during pregnancy progression and gestational complications, but it remains infeasible to noninvasively delineate placental cellular dynamics and dysfunction at the cellular level using maternal cell-free nucleic acid analysis. In this study, we addressed this issue by first dissecting the cellular heterogeneity of the human placenta and defined individual cell-type-specific gene signatures by analyzing more than 24,000 nonmarker selected cells from full-term and early preeclamptic placentas using large-scale microfluidic single-cell transcriptomic technology. Our dataset identified diverse cellular subtypes in the human placenta and enabled reconstruction of the trophoblast differentiation trajectory. Through integrative analysis with maternal plasma cell-free RNA, we resolved the longitudinal cellular dynamics of hematopoietic and placental cells in pregnancy progression. Furthermore, we were able to noninvasively uncover the cellular dysfunction of extravillous trophoblasts in early preeclamptic placentas. Our work showed the potential of integrating transcriptomic information derived from single cells into the interpretation of cell-free plasma RNA, enabling the noninvasive elucidation of cellular dynamics in complex pathological conditions.