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

The human placenta is a dynamic and cellular heterogeneous organ, which is critical in fetomaternal homeostasis and the development of preeclampsia. Previous work has shown that placenta-derived cell-free RNA increases during pregnancy. We applied large-scale microfluidic single-cell transcriptomic technology to comprehensively characterize cellular heterogeneity of the human placentas and identified multiple placental cell-type–specific gene signatures. Analysis of the cellular signature expression in maternal plasma enabled noninvasive delineation of the cellular dynamics of the placenta during pregnancy and the elucidation of extravillous trophoblastic dysfunction in early preeclampsia.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 14 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001003705	10 single-cell placental RNA libraries were generated using the Chromium Single Cell 3′ Reagent Kit (10X Genomics). All single-cell libraries were sequenced with a customized paired end with dual indexing (98/14/8/10-bp) format according to the recommendation by 10X Genomics. The data were aligned using the Cell Ranger Single-Cell Software Suite (version 1.0). Moreover, plasma RNA from 22 samples were extracted using the RNeasy Mini Kit (Qiagen). cDNA reverse transcription, second-strand synthesis, and RNA-sequencing (RNA-seq) library construction were performed using the Ovation RNA-seq System V2 (NuGEN) kit according to the manufacturer’s protocol. For alignment of the plasma RNA library, adaptor sequences and low-quality bases on the fragment ends (i.e., quality score < 5) were trimmed, and reads were aligned to the human reference genome (hg19) using the TopHat (v2.0.4) software. All aligned reads were deposited in bam file format.	Illumina HiSeq 2000 NextSeq 500	32

Publications	Citations
Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics. Tsang JCH, Vong JSL, Ji L, Poon LCY, Jiang P, Lui KO, Ni YB, To KF, Cheng YKY, Chiu RWK, Lo YMD. Proc Natl Acad Sci U S A 114: 2017 E7786-E7795	233
Current approaches and developments in transcript profiling of the human placenta. Yong HEJ, Chan SY. Hum Reprod Update 26: 2020 799-840	45
MAAPER: model-based analysis of alternative polyadenylation using 3' end-linked reads. Li WV, Zheng D, Wang R, Tian B. Genome Biol 22: 2021 222	21
Transcriptomic Drivers of Differentiation, Maturation, and Polyploidy in Human Extravillous Trophoblast. Morey R, Farah O, Kallol S, Requena DF, Meads M, Moretto-Zita M, Soncin F, Laurent LC, Parast MM. Front Cell Dev Biol 9: 2021 702046	31
Human placental biology at single-cell resolution: a contemporaneous review. Barrozo ER, Aagaard KM. BJOG 129: 2022 208-220	19
The Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target? Broekhuizen M, Danser AHJ, Reiss IKM, Merkus D. Int J Environ Res Public Health 18: 2021 11545	36
A cost-effective machine learning-based method for preeclampsia risk assessment and driver genes discovery. Wang H, Zhang Z, Li H, Li J, Li H, Liu M, Liang P, Xi Q, Xing Y, Yang L, Zuo Y. Cell Biosci 13: 2023 41	31
Histopathologic and Transcriptomic Profiling Identifies Novel Trophoblast Defects in Patients With Preeclampsia and Maternal Vascular Malperfusion. Horii M, To C, Morey R, Jacobs MB, Li Y, Nelson KK, Meads M, Siegel BA, Pizzo D, Adami R, Zhang-Rutledge K, Lamale-Smith L, Laurent LC, Parast MM. Mod Pathol 36: 2023 100035	14
Placental cell type deconvolution reveals that cell proportions drive preeclampsia gene expression differences. Campbell KA, Colacino JA, Puttabyatappa M, Dou JF, Elkin ER, Hammoud SS, Domino SE, Dolinoy DC, Goodrich JM, Loch-Caruso R, Padmanabhan V, Bakulski KM. Commun Biol 6: 2023 264	44
SARS-CoV-2 niches in human placenta revealed by spatial transcriptomics. Barrozo ER, Seferovic MD, Castro ECC, Major AM, Moorshead DN, Jochum MD, Rojas RF, Shope CD, Aagaard KM. Med 4: 2023 612-634.e4	21
Revealing the molecular landscape of human placenta: a systematic review and meta-analysis of single-cell RNA sequencing studies. Derisoud E, Jiang H, Zhao A, Chavatte-Palmer P, Deng Q. Hum Reprod Update 30: 2024 410-441	27
Placental Origins of Preeclampsia: Insights from Multi-Omic Studies. Cao C, Saxena R, Gray KJ. Int J Mol Sci 25: 2024 9343	6
An update review of the application of single-cell RNA sequencing in pregnancy-related diseases. Zhou Z, Yang X. Front Endocrinol (Lausanne) 15: 2024 1415173	2
Single-cell RNA-seq data have prevalent blood contamination but can be rescued by Originator, a computational tool separating single-cell RNA-seq by genetic and contextual information. Unjitwattana T, Huang Q, Yang Y, Tao L, Yang Y, Zhou M, Du Y, Garmire LX. Genome Biol 26: 2025 52	0