Data-Mining Approach on Transcriptomics and Methylomics Placental Analysis Highlights Genes in Fetal Growth Restriction

Chabrun, Floris; Huetz, Noémie; Dieu, Xavier; Rousseau, Guillaume; Bouzillé, Guillaume; Barca, Juan Manuel Chao de la; Procaccio, Vincent; Lenaers, Guy; Blanchet, Odile; Legendre, Guillaume; Mirebeau‐Prunier, Delphine; Cuggia, Marc; Guardiola, Philippe; Reynier, Pascal; Gascoin, Géraldine

doi:10.3389/fgene.2019.01292

Cited by 15 publications

(9 citation statements)

References 64 publications

(63 reference statements)

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“…All participants provided written informed consent prior to inclusion. The study was conducted in accordance with the declaration of Helsinki (Chabrun et al 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Alternative splicing in normal and pathological human placentas is correlated to genetic variants

et al. 2021

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Two major obstetric diseases, preeclampsia (PE), a pregnancy-induced endothelial dysfunction leading to hypertension and proteinuria, and intra-uterine growth-restriction (IUGR), a failure of the fetus to acquire its normal growth, are generally triggered by placental dysfunction. Many studies have evaluated gene expression deregulations in these diseases, but none has tackled systematically the role of alternative splicing. In the present study, we show that alternative splicing is an essential feature of placental diseases, affecting 1060 and 1409 genes in PE vs controls and IUGR vs controls, respectively, many of those involved in placental function. While in IUGR placentas, alternative splicing affects genes specifically related to pregnancy, in preeclamptic placentas, it impacts a mix of genes related to pregnancy and brain diseases. Also, alternative splicing variations can be detected at the individual level as sharp splicing differences between different placentas. We correlate these variations with genetic variants to define splicing Quantitative Trait Loci (sQTL) in the subset of the 48 genes the most strongly alternatively spliced in placental diseases. We show that alternative splicing is at least partly piloted by genetic variants located either in cis (52 QTL identified) or in trans (52 QTL identified). In particular, we found four chromosomal regions that impact the splicing of genes in the placenta. The present work provides a new vision of placental gene expression regulation that warrants further studies.

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“…All participants provided written informed consent prior to inclusion. The study was conducted in accordance with the declaration of Helsinki (Chabrun et al 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Alternative splicing in normal and pathological human placentas is correlated to genetic variants

et al. 2021

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“…They built machine learning models that had a high capacity for predicting PTB, with r 2 of 0.83 between the predicted and the actual PTB score. ( 184 ) Ghaemi et al, in 51 samples from 17 pregnant women who delivered at term, built multivariate predictive models for gestational age using the Elastic net algorithm to integrate the multi-omics datasets including transcriptomics, microbiomics, proteomics and metabolomics, which can significantly increase predictive power compared to models based on single-omics datasets. ( 185 ) However, as with the other types of studies reviewed above, these currently available studies had limited samples sizes, and their findings call for replication in large populations.…”

Section: Recent Advances In Multi-omics Studies Of Ptbmentioning

confidence: 99%

Gaining a deeper understanding of social determinants of preterm birth by integrating multi-omics data

2020

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In the US, high rates of preterm birth (PTB) and profound Black-White disparities in PTB have persisted for decades. This review focuses on the role of social determinants of health (SDH), with an emphasis on maternal stress, in PTB disparity and biological embedding. It covers: 1) PTB disparity in US Black women and possible contributors; 2) The role of SDH, highlighting maternal stress, in the persistent racial disparity of PTB; 3) Epigenetics at the interface between genes and environment; 4) The role of the genome in modifying maternal stress-PTB associations; 5) Recent advances in multi-omics studies of PTB; and 6) Future perspectives on integrating multi-omics with SDH to elucidate the Black-White disparity in PTB. Available studies have indicated that neither environmental exposures nor genetics alone can adequately explain the Black-White PTB disparity. Preliminary yet promising findings of epigenetic and gene-environment interaction studies underscore the value of integrating SDH with multi-omics in prospective birth cohort studies, especially among high-risk Black women. In an era of rapid advancements in biomedical sciences and technologies and a growing number of prospective birth cohort studies, we have unprecedented opportunities to advance this field and finally address the long history of health disparities in PTB.

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“…Genome-wide transcriptomic and epigenomic studies have greatly contributed to the understanding of the molecular mechanisms involved in either normal or pathological placenta development. Thus, numerous studies have revealed altered placental expression of various genes in PE and IUGR ( Cox et al, 2015 ; Deyssenroth et al, 2017 ; Chabrun et al, 2019 ; Majewska et al, 2019 ; Benny et al, 2020 ). A particular category concerns those genes encoding for non-protein coding RNAs (ncRNAs).…”

Section: Introductionmentioning

confidence: 99%

Urothelial Cancer Associated 1 (UCA1) and miR-193 Are Two Non-coding RNAs Involved in Trophoblast Fusion and Placental Diseases

Apicella

Jacques

Gascoin

et al. 2021

Front. Cell Dev. Biol.

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A bioinformatics screen for non-coding genes was performed from microarrays analyzing on the one hand trophoblast fusion in the BeWo cell model, and on the other hand, placental diseases (preeclampsia and Intra-Uterine Growth Restriction). Intersecting the deregulated genes allowed to identify two miRNA (mir193b and miR365a) and one long non-coding RNA (UCA1) that are pivotal for trophoblast fusion, and deregulated in placental diseases. We show that miR-193b is a hub for the down-regulation of 135 cell targets mainly involved in cell cycle progression and energy usage/nutrient transport. UCA1 was explored by siRNA knock-down in the BeWo cell model. We show that its down-regulation is associated with the deregulation of important trophoblast physiology genes, involved in differentiation, proliferation, oxidative stress, vacuolization, membrane repair and endocrine production. Overall, UCA1 knockdown leads to an incomplete gene expression profile modification of trophoblast cells when they are induced to fuse into syncytiotrophoblast. Then we performed the same type of analysis in cells overexpressing one of the two major isoforms of the STOX1 transcription factor, STOX1A and STOX1B (associated previously to impaired trophoblast fusion). We could show that when STOX1B is abundant, the effects of UCA1 down-regulation on forskolin response are alleviated.

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Data-Mining Approach on Transcriptomics and Methylomics Placental Analysis Highlights Genes in Fetal Growth Restriction

Cited by 15 publications

References 64 publications

Alternative splicing in normal and pathological human placentas is correlated to genetic variants

Alternative splicing in normal and pathological human placentas is correlated to genetic variants

Gaining a deeper understanding of social determinants of preterm birth by integrating multi-omics data

Urothelial Cancer Associated 1 (UCA1) and miR-193 Are Two Non-coding RNAs Involved in Trophoblast Fusion and Placental Diseases

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