Placental trophoblast cell differentiation: Physiological regulation and pathological relevance to preeclampsia

Ji, Lei; Brkić, Jelena; Liu, Ming; Fu, Guodong; Peng, Chun; Wang, Yanling

doi:10.1016/j.mam.2012.12.008

Cited by 314 publications

(268 citation statements)

References 530 publications

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“…The high number of trophoblast cells recovered in our dataset allowed computational reconstruction of the trophoblastic differentiation trajectories and identification of highly specific cell signature genes. Our analysis supported a bifurcating model with VCTB differentiating bidirectionally into SCTB and EVTB (64). The trajectories recapitulated many known regulator interactions during trophoblast development and discovered potential players that laid a foundation for future investigation.…”

Section: Discussionsupporting

confidence: 62%

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

Tsang

Vong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

248

261

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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. single-cell transcriptomics | cell-free RNA | noninvasive prenatal testing | placenta | preeclampsia

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Section: Discussionsupporting

confidence: 62%

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

Tsang

Vong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

248

261

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“…These include fetal weight restriction and low fetal birth weight (intrauterine growth retardation or IUGR), [81][82][83][84] toxin exposures such as environmental toxins, 85,86 cancer (hepatocellular carcinoma), 87 diabetes mellitus 88 and, the most heavily studied, human pre-eclampsia. 79,[89][90][91][92][93][94][95][96] Many of the pre-eclampsia studies have investigated miRNA expression using high throughput microarray, and qPCR (primarily in order to validate specific microarray findings). Previous studies have established that oxygen tension is implicated in placental development in humans and mice.…”

Section: Microrna Regulation In the Placentamentioning

confidence: 99%

MicroRNAs, immune cells and pregnancy

et al. 2014

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MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs that are expressed in many cell types, where they regulate the expression of complementary RNAs, thus modulating the stability and translation of mRNAs. miRNAs are predicted to regulate the expression of ,50% of all protein coding genes in mammals. Therefore, they participate in virtually all cellular processes investigated so far. Altered miRNAs expressions are associated with both physiological (pregnancy) and pathological processes (cancer). As the dynamic maternal-fetal interface plays a critical role in the maintenance of successful pregnancy, it is not surprising that the miRNAs that are unique to reproductive tissues are abundantly expressed. Research in this field has demonstrated the presence and dysregulation of a distinct set of pregnancy-associated miRNAs; however, most studies have centered on localizing various miRNAs in reproductive microdomains associated with normal or complicated pregnancies. Although several independent miRNA regulatory mechanisms associated with endometrial receptivity, immune cells, angiogenesis and placental development have been studied, miRNA-mediated regulation of pregnancy remains poorly understood. This review provides a summary of the current data on miRNA regulation as well as functional profiles of miRNAs that are found in the uterus, in immune cells associated with maternal tolerance to the fetus, and those involved in angiogenesis and placental development.

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“…Diploid EVTs located in the proximal cell column continuously proliferate to provide a constant supply of invading EVTs during the first trimester of pregnancy. [1][2][3][4] To establish a connection between the placenta and the maternal vasculature, terminal differentiated trophoblast giant cells, characterized by endoreduplication up to 1000N of DNA, 5 invade and transform the maternal vessels, and this transformation in turn guarantees nutrition and oxygen support to the placenta and the fetus. 6,7 Before differentiating into the invasive pathway, the proliferative trophoblast cells of the cell column escape from the cell cycle when they come into contact with the maternal decidua.…”

Section: Introductionmentioning

confidence: 99%

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

Kipkeew

Kirsch

Klein

et al. 2016

Cell Adhesion & Migration

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Placental trophoblast cell differentiation: Physiological regulation and pathological relevance to preeclampsia

Cited by 314 publications

References 530 publications

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

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

MicroRNAs, immune cells and pregnancy

CCN1 (CYR61) and CCN3 (NOV) signaling drives human trophoblast cells into senescence and stimulates migration properties

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