Biology subjects

Rolland, A.

Publications and source records attributed to Rolland, A..

4 recordsLinked to original sources

bioRxiv2026

An integrated multimodal pan-organ atlas of the female reproductive system across the lifespan contextualises gynaecological pathologies

Single cell transcriptomics has transformed our knowledge of reproductive tissues, yet studies remain largely organ-specific and temporally limited, leaving an incomplete picture of how cell types are distributed across the reproductive system over a lifetime. Gynaecological conditions affect more than one in four females and frequently span multiple organs and life stages. To advance our understanding and treatment of these conditions, an integrated cellular reference is essential. Here we present the Human Female Reproductive System Cell Atlas v1: a single-cell transcriptomic resource integrating more than 2M cells across the ovary, fallopian tube, uterus, cervix and vagina over the lifespan and menstrual cycle, further integrated with spatial transcriptomics and chromatin accessibility profiling to define 210 cell types through community-based annotation. Cross-organ integration resolves shared and organ-specific cellular states, identifying uterine-specific perivascular populations lining uterine spiral arteries, hypoxia-sensing type 3 innate lymphoid cells (ILC3s) enriched in the uterus, and lipid-associated macrophages with distinct subsets in each reproductive organ, including a previously undescribed population shared between the uterus and fallopian tube. Cross-organ integration enables detection of ectopic epithelial populations in otherwise healthy donors, including endometrial-like cells within a paediatric ovary consistent with early endometriosis. Integration with genome-wide association studies (GWAS) reveals that risk variants for major gynecological conditions act in mesenchymal cell states defined by specific transcriptional programmes and spatial or temporal context - for instance, heavy menstrual bleeding risk is enriched in basal fibroblasts (SFRP5) of the regenerative endometrial compartment. An integrated chromatin accessibility atlas provides peak-to-gene maps across reproductive cell types, enabling nomination of disease effector genes and providing the first regulatory evidence linking a Polyendocrine Metabolic Ovarian Syndrome (PMOS) risk locus to INHBB in granulosa cells. Together, this resource establishes a cellular and molecular framework for reproductive biology and the pathogenesis of neglected gynaecological conditions.

Cell Biology↗

bioRxiv2024

Unexplored Yeast diversity in Seed Microbiota

Yeasts are known to be fantastic biotechnological resources for medical, food, and industrial applications, but their potential remains untapped in agriculture, especially for plant biostimulation and biocontrol. In particular, yeasts have been reported as part of the core microbiome of seeds using next generation sequencing methods, but their diversity and functional roles remain largely undescribed. Focusing on yeasts and excluding filamentous fungi, this study aimed to characterize the diversity of seed-associated yeasts across nine plant species (crops and non-cultivated species) using culturomics and microscopy. Comparison with available metabarcoding data was performed to assess the representativeness of the strain collection in seed samples. Our results show that seed-associated yeasts largely belong to Basidiomycota phylum and more particularly to the Tremellomycetes class. This yeast collection covers 15 genera (2 of Ascomycota and 13 of Basidiomycota). Out of the 229 isolates described, the most frequently isolated yeasts were Holtermanniella, Vishniacozyma, Filobasidium, Naganishia and Sporobolomyces. The yeasts from these dominant genera were isolated from multiple plant species (4 to 8), except for Naganishia which only originated from Solanum lycopersicum L. These results are also consistent with the fact that these dominant taxa were recently identified as members of the core seed microbiome, indicating their high prevalence and abundance across diverse plant hosts and environments. Compared to previous plant yeast diversity surveys, the members from Ascomycota yeasts are less frequent in seeds and only represented here by the Aureobasidium and Taphrina genera. Altogether, these results suggest that yeasts are generally well-adapted to the aboveground habitats of plants, but seeds represent a specific habitat that diverse Basidiomycota yeasts can colonize. Take away messageO_LI229 yeasts isolated from seeds and seedlings of diverse plant species C_LIO_LIMost isolates are Basidiomycota yeasts, especially of the Tremellomycetes class C_LIO_LIThe most frequently isolated yeasts belong to Holtermanniella, Vishniacozyma, Filobasidium and Sporobolomyces genera C_LIO_LIThe collection is representative of taxa found in seed microbiota of multiple plant species, including core members C_LI

microbiology↗

bioRxiv2020

Human USP18 is regulated by miRNAs via the 3'UTR, a sequence duplicated in lincRNA genes residing in chr22q11.21

Ubiquitin-specific peptidase 18 (USP18) acts as gatekeeper of type I interferon (IFN) responses by binding to the IFN receptor subunit IFNAR2 and preventing activation of the downstream JAK/STAT pathway. In any given cell type, the level of USP18 is a key determinant of the output of interferon-stimulated transcripts. How the baseline level of USP18 is finely tuned in different cell types remains ill defined. Here we explored post-transcriptional regulation of USP18 by microRNAs (miRNAs) and identified four miRNAs (miR-24-3p, miR-191-5p, miR-423-5p and miR-532-3p) that efficiently target USP18 through binding to the 3UTR. Among these, three miRNAs are particularly enriched in circulating monocytes which exhibit low baseline USP18. Intriguingly, the USP18 3UTR sequence is duplicated in human and chimpanzee genomes. In human, we found several copies of the 3UTR that are embedded in long intergenic non-coding (linc) RNA genes residing in chr22q11.21 and exhibiting a tissue-specific expression pattern. Interestingly, one of these lincRNAs (here named linc-UR-B1) is uniquely and highly expressed in testis. RNA-seq data analyses from testicular cell subsets revealed a positive correlation between linc-UR-B1 and USP18 expression in spermatocytes and spermatids. Overall, our findings uncover a set of miRNAs and lincRNAs, which may be part of a network evolved to fine-tune baseline USP18, particularly in cell types where IFN responsiveness needs to be tightly controlled. SIGNIFICANT STATEMENTUSP18 is a non-redundant negative feedback regulator of type I IFN signaling and a key determinant of cell responsiveness to IFN. How baseline USP18 is set in different human cell types is ill defined. We identified three microRNAs that restrain USP18 level notably in primary monocytes through binding the 3UTR. We found several copies of the USP18 3UTR embedded in long intergenic non-coding (linc) RNAs which reside in a complex region of human chromosome 22. These lincRNAs are expressed in a tissue-specific manner. We describe one lincRNA expressed only in testis, and most notably in germ cells. Correlative analyses suggest that microRNAs and lincRNAs may form a network controlling baseline USP18 and IFN responsiveness.

immunology↗

bioRxiv2020

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

Viruses have colonized the germ line of our ancestors at several occasions during evolution, leading to the integration in the human genome of viral sequences from over 30 retroviral groups and a few non-retroviruses. Among the recently emerged viruses infecting humans, several target the testis (eg HIV, Zika and Ebola viruses). Here we aimed to investigate whether human testicular germ cells (TGCs) can support integration by HIV, a contemporary retrovirus that started to spread in the human population during the last century. We report that albeit alternative receptors enabled HIV-1 binding to TGCs, HIV virions failed to infect TGCs in vitro. Nevertheless, exposure of TGCs to infected lymphocytes, naturally present in the testis from HIV+ men, led to HIV-1 entry, integration and early protein expression. Similarly, cell-associated infection or bypassing viral entry led to HIV-1 integration in a spermatogonial cell line. Using DNAscope, HIV-1 and SIV DNA were detected within a few TGCs in the testis from one infected patient, one rhesus macaque and one African Green monkey in vivo. Molecular landscape analysis revealed that early TGCs were enriched in HIV early co-factors up to integration and had overall low antiviral defenses when compared with testicular macrophages and Sertoli cells. In conclusion, our study reveals that TGCs can support the entry and integration of HIV upon cell-associated infection. This could represent a way for this contemporary virus to integrate our germline and become endogenous in the future, as happened during human evolution for a number of viruses. ImportanceViruses have colonized the host germ line at many occasions during evolution to eventually become endogenous. Here we aimed at investigating whether human testicular germ cells (TGCs) can support such viral invasion by studying HIV interactions with TGCs in vitro. Our results indicate that isolated primary TGCs express alternative HIV-1 receptors allowing virions binding but not entry. However, HIV-1 entered and integrated in TGCs upon cell-associated infection, and produced low level of viral proteins. In vivo, HIV-1 and SIV DNA was detected in a few TGCs. Molecular landscape analysis showed that TGCs have overall weak antiviral defenses. Altogether, our results indicate that human TGCs can support HIV-1 early replication including integration, suggesting potential for endogenization in the future generations.

microbiology↗