A novel human endogenous retroviral protein inhibits cell-cell fusion

Sugimoto, Jun; Sugimoto, Makiko; Bernstein, Helene B.; Jinno, Yoshihiro; Schust, Danny J.

doi:10.1038/srep01462

Cited by 92 publications

(109 citation statements)

References 43 publications

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“…In contrast, another ERV transcript, ERVH48-1, is depleted in SCTBs (Fig. 2B), concordant with a recent report that it functions as an inhibitor of syncytium formation in VCTBs (35). To further study the cell fusion process, we identified genes that showed variation similar to ERVFRD-1 along the SCTB pathway (Fig.…”

Section: Resultssupporting

confidence: 87%

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.

265

267

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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: Resultssupporting

confidence: 87%

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.

265

267

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“…ERVFRD-1 has been proposed to be immunosuppressive, an activity not shared by ERVW-1 (Mangeney, et al 2007). Several other ERV proteins, e.g.ERV3-1, and ERVK family members, including an antagonist of cell fusion (Sugimoto, et al 2013) are expressed in the placenta, but roles for most are even more obscure than that of ERVFRD-1.…”

Section: Evolution Of Placenta Specific Genesmentioning

confidence: 99%

The evolution of the placenta

Roberts¹,

Green²,

Schulz³

2016

Reproduction

174

125

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The still apt definition of a placenta is that coined by Mossman, namely apposition or fusion of the fetal membranes to the uterine mucosa for physiological exchange. As such it is a specialized organ whose purpose is to provide continuing support to the developing young. By this definition, placentas have evolved within every vertebrate class other than birds. They have evolved on multiple occasions, often within quite narrow taxonomic groups. As the placenta and the maternal system associate more intimately, such that the conceptus relies extensively on maternal support, the relationship leads to increased conflict that drives adaptive changes on both sides. The story of vertebrate placentation, therefore, is one of convergent evolution at both the macro- and molecular levels. In this short review, we first describe the emergence of placental-like structures in non-mammalian vertebrates and then transition to mammals themselves. We close the review by discussing mechanisms that might have favored diversity and hence evolution of the morphology and physiology of the placentas of eutherian mammals.

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“…Given this hypomethylation of LTRs in placentas, it is not surprising that numerous sub-families of ERV proviruses are expressed within human placental tissues. More specifically, there is evidence of proviral transcription from ERV-E (Yi and Kim, 2007), ERV3 (ERV-R; Boyd et al, 1993; Andersson et al, 2005), ERV-K (Kammerer et al, 2011), ERV-fb1 (Sugimoto et al, 2013), ERV-V1/2 (Esnault et al, 2013), ERV-W (Blond et al, 2000), and ERV-FRD (Blaise et al, 2003; Supplementary Tables 1, 2). …”

Section: Ervs In the Placentamentioning

confidence: 99%

Endogenous Retroviruses: With Us and against Us

et al. 2017

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Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe how disruption of the regulated mechanisms of ERVs may impact somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.

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A novel human endogenous retroviral protein inhibits cell-cell fusion

Cited by 92 publications

References 43 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

The evolution of the placenta

Endogenous Retroviruses: With Us and against Us

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