The ReproGenomics Viewer: an integrative cross-species toolbox for the reproductive science community

Darde, Thomas Alain; Sallou, Olivier; Becker, E.; Evrard, Bertrand; Monjeaud, Cyril; Bras, Yvan Le; Jégou, Bernard; Collin, Olivier; Rolland, Antoine; Chalmel, Frédéric

doi:10.1093/nar/gkv345

Cited by 48 publications

(45 citation statements)

References 51 publications

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“…from epigenomic, regulomic, transcriptomic, proteomic, and interactomic studies, in order to link the flow of information from DNA to functional proteins and non-coding RNAs. The success of this integrative work will also depend on the development of new types of web servers, such as the ReproGenomics Viewer (http:// rgv.genouest.org/; Darde et al 2015), which allows the visualization, mining, and comparison of various types of omics data (e.g. ChIP-seq, RNA-seq, MS-based proteomics) in a multi-and cross-species manner.…”

Section: Resultsmentioning

confidence: 99%

Linking transcriptomics and proteomics in spermatogenesis

Chalmel¹,

Rolland²

2015

Reproduction

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Spermatogenesis is a complex and tightly regulated process leading to the continuous production of male gametes, the spermatozoa. This developmental process requires the sequential and coordinated expression of thousands of genes, including many that are testisspecific. The molecular networks underlying normal and pathological spermatogenesis have been widely investigated in recent decades, and many high-throughput expression studies have studied genes and proteins involved in male fertility. In this review, we focus on studies that have attempted to correlate transcription and translation during spermatogenesis by comparing the testicular transcriptome and proteome. We also discuss the recent development and use of new transcriptomic approaches that provide a better proxy for the proteome, from both qualitative and quantitative perspectives. Finally, we provide illustrations of how testis-derived transcriptomic and proteomic data can be integrated to address new questions and how the 'proteomics informed by transcriptomics' technique, by combining RNA-seq and MS-based proteomics, can contribute significantly to the discovery of new protein-coding genes or new protein isoforms expressed during spermatogenesis.Reproduction (2015) 150 R149-R157

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Section: Resultsmentioning

confidence: 99%

Linking transcriptomics and proteomics in spermatogenesis

Chalmel¹,

Rolland²

2015

Reproduction

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“…Single-cell RNA-sequencing data of human adult testicular cells [84] were recovered from the ReproGenomics Viewer [85,86] and processed using the AMEN software [87]. Briefly, out of the 23’109 genes measured in this experiment, only those with an average expression level (log2[count+1]) of at least 1 in a least one cell population and a fold-change of at least 2 between at least two cell populations were considered as being differentially-expressed.…”

Section: Methodsmentioning

confidence: 99%

Potential for virus endogenization in humans through testicular germ cell infection: the case of HIV

Mahé

Matusali

Deléage

et al. 2020

Preprint

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30Viruses have colonized the germ line of our ancestors at several occasions during evolution, 31 leading to the integration in the human genome of viral sequences from over 30 retroviral 32 groups and a few non-retroviruses. Among the recently emerged viruses infecting humans, 33 several target the testis (eg HIV, Zika and Ebola viruses). Here we aimed to investigate whether 34 human testicular germ cells (TGCs) can support integration by HIV, a contemporary retrovirus 35 that started to spread in the human population during the last century. We report that albeit 36 alternative receptors enabled HIV-1 binding to TGCs, HIV virions failed to infect TGCs in 37 vitro. Nevertheless, exposure of TGCs to infected lymphocytes, naturally present in the testis 38 from HIV+ men, led to HIV-1 entry, integration and early protein expression. Similarly, cell-39 associated infection or bypassing viral entry led to HIV-1 integration in a spermatogonial cell 40 line. Using DNAscope, HIV-1 and SIV DNA were detected within a few TGCs in the testis 41 from one infected patient, one rhesus macaque and one African Green monkey in vivo. 42 Molecular landscape analysis revealed that early TGCs were enriched in HIV early co-factors 43 up to integration and had overall low antiviral defenses when compared with testicular 44 macrophages and Sertoli cells. In conclusion, our study reveals that TGCs can support the entry 45 and integration of HIV upon cell-associated infection. This could represent a way for this 46 contemporary virus to integrate our germline and become endogenous in the future, as happened 47 Importance 52 Viruses have colonized the host germ line at many occasions during evolution to eventually 53 become endogenous. Here we aimed at investigating whether human testicular germ cells 54 (TGCs) can support such viral invasion by studying HIV interactions with TGCs in vitro. Our 55 results indicate that isolated primary TGCs express alternative HIV-1 receptors allowing virions 56 binding but not entry. However, HIV-1 entered and integrated in TGCs upon cell-associated 57 infection, and produced low level of viral proteins. In vivo, HIV-1 and SIV DNA was detected 58 in a few TGCs. Molecular landscape analysis showed that TGCs have overall weak antiviral 59 defenses. Altogether, our results indicate that human TGCs can support HIV-1 early replication 60 including integration, suggesting potential for endogenization in the future generations. 61 62 63 Retroviruses have repeatedly infected the germline during our evolution and integrated their 64 DNA into the host genome , which has been passed on to the next generations by Mendelian 65 inheritance [1,2]. When not detrimental, the integration of viral sequences has led to their 66 fixation and endogenization in the population [3]. Thus, about 8% of the human genome is now 67 composed of endogenous retroviruses (ERVs), representing 31 distinct viral groups [2]. Such 68 integration, still ongoing in mammals [4], has driven the acquisition of new functions in the 69 host,...

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“…Gene lists were analyzed for enrichment using the online tool EnrichR 67 . The ChIP-seq data are available in the ReproGenomics Viewer (https://rgv.genouest.org) 68, 69 and Gene Expression Omnibus (GSE128767; http://www.ncbi.nlm.nih.gov/geo/).…”

Section: Methodsmentioning

confidence: 99%

RUNX1 safeguards the identity of the fetal ovary through an interplay with FOXL2

Nicol

Grimm

Chalmel

et al. 2019

Preprint

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ovary, cell fate, disorders of sex development, sex reversal 20 21 22 A critical step that shapes the reproductive identity of the embryo is the sexual 37 differentiation of the bipotential gonads. Supporting cells in the fetal gonads are the first 38 cell population to differentiate, and dictate the fate of the gonads. As a consequence, 39 defects in supporting cell differentiation have dire consequences on reproductive 40 outcomes of the individual, from sex-reversal to infertility. Supporting cells differentiate 41 into either Sertoli cells, which drive testis development, or granulosa cells, which control 42 ovarian development. It has become clear that supporting cell differentiation, and 43 maintenance of their commitment, requires a coordinated action of multiple factors that 44 play either complementary, redundant and even antagonistic roles 1 . For instance, fate 45 decision and maintenance of ovarian identity relies mainly on two conserved elements: 46 the WNT4/RSPO1/beta-catenin pathway 2, 3, 4 and the transcription factor FOXL2 5, 6, 7 . 47In this study, we set up to investigate the role of transcription factor RUNX1 in the 59 mouse fetal ovary. In Drosophila melanogaster, the RUNX ortholog runt is essential for 60 ovarian determination 21, 22 . In the mouse, Runx1 mRNA is enriched in the fetal ovary 61 based on transcriptomic analyses 23 . The RUNX family arose early in evolution 24 : 62 members have been identified in metazoans from sponge to human, where they play 63conserved key roles in developmental processes. In vertebrates, RUNX1 acts as a 64 transcription factor critical for cell lineage specification in multiple organs, and 65 particularly in cell populations of epithelial origin 25 . We first established the expression 66 profile of RUNX1 in the fetal gonads in multiple vertebrate species from fish to human. 67We then used knockout mouse models and genomic approaches to determine the 68 function and molecular action of RUNX1 and its interplay with another conserved 69 ovarian regulator, FOXL2, during supporting cell differentiation in the fetal ovary. 70 71

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The ReproGenomics Viewer: an integrative cross-species toolbox for the reproductive science community

Cited by 48 publications

References 51 publications

Linking transcriptomics and proteomics in spermatogenesis

Linking transcriptomics and proteomics in spermatogenesis

Potential for virus endogenization in humans through testicular germ cell infection: the case of HIV

RUNX1 safeguards the identity of the fetal ovary through an interplay with FOXL2

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