Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

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 significan...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2017-09, Vol.114 (37), p.E7786-E7795
Main Authors: Tsang, Jason C. H., Vong, Joaquim S. L., Ji, Lu, Poon, Liona C. Y., Jiang, Peiyong, Lui, Kathy O., Ni, Yun-Bi, To, Ka Fai, Cheng, Yvonne K. Y., Chiu, Rossa W. K., Lo, Yuk Ming Dennis
Format: Article
Language:English
Subjects:
Biological Sciences
Cell-Free Nucleic Acids - analysis
Cell-Free Nucleic Acids - blood
Cell-Free Nucleic Acids - metabolism
Cellular biology
Complications
Differentiation
Dynamics
Female
Fetuses
Humans
Microfluidic Analytical Techniques - methods
Microfluidics
Nucleic acids
Placenta
Placenta - metabolism
Placenta - physiology
Plasma - metabolism
PNAS Plus
Pre-eclampsia
Pre-Eclampsia - genetics
Preeclampsia
Pregnancy
Pregnancy complications
Ribonucleic acid
RNA
RNA - analysis
RNA - blood
Single-Cell Analysis - methods
Studies
Tissue analysis
Trajectory analysis
Transcriptome - genetics
Trophoblasts
Trophoblasts - metabolism
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1710470114