Imprinted MicroRNA Gene Clusters in the Evolution, Development, and Functions of Mammalian Placenta

Malnou, Cécile E.; Umlauf, David; Mouysset, Maïlys; Cavaillé, Jérôme

doi:10.3389/fgene.2018.00706

Cited by 74 publications

(79 citation statements)

References 140 publications

(200 reference statements)

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“…In addition to the identi cation of population and SON effects, our data allowed us to examine a wellcharacterized phenomenon of imprinted miRNA expression in the human placenta [31]. Previously reported imprinted expression of the miRNA cluster located on chromosome 19 (C19MC) [31,32] was also evident in our data. Previous work further linked the amplitude of the imprinting effect with the mother's BMI [48].…”

Section: Discussionsupporting

confidence: 58%

“…One of the characteristic features of placental miRNA is the prevalence of imprinted expression, a term referring to complete or partial suppression of one of the parental alleles [31]. To assess the extent of miRNA expression imprinting in our data, we focused on the largest characterized imprinted miRNA cluster, located on chromosome 19 (C19MC) and expressed almost exclusively in the placenta [32].…”

Section: Expression Of Imprinted Mirnamentioning

confidence: 99%

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Variation of MicroRNA Expression in the Human Placenta Driven by Population Identity and Sex of the Newborn

Guo

Huang

Jiang

et al. 2020

Preprint

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BackgroundAnalysis of lymphocyte cell lines revealed substantial differences in the expression of mRNA and microRNA (miRNA) among human populations. The extent of such population-associated differences in actual human tissues remains largely unexplored. The placenta is one of the few solid human tissues that can be collected in substantial numbers in a controlled manner, enabling quantitative analysis of transient biomolecules such as RNA transcripts. Here, we analyzed microRNA (miRNA) expression in human placental samples derived from 36 individuals representing four genetically distinct human populations: African Americans, European-Americans, South Asians, and East Asians. All samples were collected at the same hospital following a unified protocol, thus minimizing potential biases that might influence the results.ResultsSequence analysis of the miRNA fraction yielded 938 annotated and 70 novel miRNA transcripts expressed in the placenta. Of them, 82 (9%) of annotated and 11 (16%) of novel miRNAs displayed quantitative expression differences among populations, generally reflecting reported genetic and mRNA-expression-based distances. Several co-expressed miRNA clusters stood out from the rest of the population-associated differences in terms of miRNA evolutionary age, tissue-specificity, and disease-association characteristics. Among three non-environmental influenced demographic parameters, the second largest contributor to miRNA expression variation after population was the sex of the newborn, with 32 miRNAs (3% of detected) exhibiting significant expression differences depending on whether the newborn was male or female. Male-associated miRNAs were evolutionarily younger and correlated inversely with the expression of target mRNA involved in neuron-related functions. In contrast, both male and female-associated miRNAs appeared to mediate different types of hormonal responses. Demographic factors further affected reported imprinted expression of 66 placental miRNAs: the imprinting strength correlated with the mother’s weight, but not height. ConclusionsOur results showed that among 12 assessed demographic variables, population affiliation and fetal sex had a substantial influence on miRNA expression variation among human placental samples. The effect of newborn-sex-associated miRNA differences further led to expression inhibition of the target genes clustering in specific functional pathways. By contrast, population-driven miRNA differences might mainly represent neutral changes with minimal functional impacts.

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Section: Discussionsupporting

confidence: 58%

Section: Expression Of Imprinted Mirnamentioning

confidence: 99%

Variation of MicroRNA Expression in the Human Placenta Driven by Population Identity and Sex of the Newborn

Guo

Huang

Jiang

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Considering the well-established role of C19MC in placental physiology regulating trophoblast differentiation and antiviral response [17], our results suggest a causal role of C19MC in the expressional perturbations noted.…”

Section: Plos Geneticssupporting

confidence: 52%

“…In adult tissues, C19MC miRNAs are only expressed in the placenta [16], and therefore at least theoretically make an attractive target for therapeutic intervention. In the placenta, C19MC plays a pivotal role in trophoblast differentiation and migration as well as in providing resistance to viral infection [17].…”

Section: Introductionmentioning

confidence: 99%

The genomic landscape of undifferentiated embryonal sarcoma of the liver is typified by C19MC structural rearrangement and overexpression combined with TP53 mutation or loss

et al. 2020

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Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignancy. Though the molecular underpinnings of this cancer have been largely unexplored, recurrent chromosomal breakpoints affecting a noncoding region on chr19q13, which includes the chromosome 19 microRNA cluster (C19MC), have been reported in several cases. We performed comprehensive molecular profiling on samples from 14 patients diagnosed with UESL. Congruent with prior reports, we identified structural variants in chr19q13 in 10 of 13 evaluable tumors. From whole transcriptome sequencing, we observed striking expressional activity of the entire C19MC region. Concordantly, in 7 of 7 samples undergoing miRNAseq, we observed hyperexpression of the miRNAs within this cluster to levels >100 fold compared to matched normal tissue or a non-C19MC amplified cancer cell line. Concurrent TP53 mutation or copy number loss was identified in all evaluable tumors with evidence of C19MC overexpression. We find that C19MC miRNAs exhibit significant negative correlation to TP53 regulatory miRNAs and K-Ras regulatory miRNAs. Using RNA-seq we identified that pathways relevant to cellular differentiation as well as mRNA translation machinery are transcriptionally enriched in UESL. In summary, utilizing a combination of next-generation sequencing and high-density arrays we identify the combination of C19MC

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“…The C19MC cluster, which encodes microRNAs, is paternally expressed in the trophoblast. Although these miRNAs are expressed in hESCs, expression is much higher in the trophoblast (Lee et al, 2016a;Malnou et al, 2019;Noguer-Dance et al, 2010). Apart from the C19MC cluster, several other genes that are involved in reproduction are located on chromosome 19q13.4 (Moffett and Colucci, 2015).…”

Section: Molecular Mechanisms Underpinning Human Placental Developmentmentioning

confidence: 99%

Development of the human placenta

2019

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The placenta is essential for normal in utero development in mammals. In humans, defective placental formation underpins common pregnancy disorders such as pre-eclampsia and fetal growth restriction. The great variation in placental types across mammals means that animal models have been of limited use in understanding human placental development. However, new tools for studying human placental development, including 3D organoids, stem cell culture systems and single cell RNA sequencing, have brought new insights into this field. Here, we review the morphological, molecular and functional aspects of human placental formation, with a focus on the defining cell of the placentathe trophoblast.

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Imprinted MicroRNA Gene Clusters in the Evolution, Development, and Functions of Mammalian Placenta

Cited by 74 publications

References 140 publications

Variation of MicroRNA Expression in the Human Placenta Driven by Population Identity and Sex of the Newborn

Variation of MicroRNA Expression in the Human Placenta Driven by Population Identity and Sex of the Newborn

The genomic landscape of undifferentiated embryonal sarcoma of the liver is typified by C19MC structural rearrangement and overexpression combined with TP53 mutation or loss

Development of the human placenta

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