A5076958268- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sexual Differentiation and Disorders
- Sperm and Testicular Function
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Animal Genetics and Reproduction
- Reproductive Biology and Fertility
- Genomics and Chromatin Dynamics
- Reproductive System and Pregnancy
- Cancer-related molecular mechanisms research
- Renal and related cancers
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- Testicular diseases and treatments
- RNA Research and Splicing
- RNA modifications and cancer
- Axon Guidance and Neuronal Signaling
- Cellular Mechanics and Interactions
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Hedgehog Signaling Pathway Studies
- Ovarian function and disorders
- Immune Cell Function and Interaction
- Adipose Tissue and Metabolism
- Prenatal Screening and Diagnostics
Bar-Ilan University
2023-2024
École Normale Supérieure de Lyon
2019-2024
Centre National de la Recherche Scientifique
2019-2024
Institut de Génomique Fonctionnelle de Lyon
2019-2024
Université Claude Bernard Lyon 1
2019-2024
Institut de Génétique Humaine
2023-2024
Université de Montpellier
2023-2024
University of Geneva
2014-2023
SIB Swiss Institute of Bioinformatics
2017-2019
Institut de Recherche en Informatique et Systèmes Aléatoires
2017
There are ∼650,000 Alu elements in transcribed regions of the human genome. These contain cryptic splice sites, so they constant danger aberrant incorporation into mature transcripts. Despite posing a major threat to transcriptome integrity, little is known about molecular mechanisms preventing their inclusion. Here, we present mechanism for protecting from exonization transposable elements. Quantitative iCLIP data show that RNA-binding protein hnRNP C competes with splicing factor U2AF65 at...
Tracking neuronal transcriptional programs Early in brain development, cortical neurons are born near the ventricles, then migrate to their functional destinations. Telley et al. used a fluorescent labeling technique see what transcripts characterize these earliest stages of neural development. Waves initiated, passed by as neuron progresses from proliferative migratory and finally connectivity phases. Science , this issue p. 1443
Sex determination is a unique process that allows the study of multipotent progenitors and their acquisition sex-specific fates during differentiation gonad into testis or an ovary. Using time series single-cell RNA sequencing (scRNA-seq) on ovarian Nr5a1-GFP+ somatic cells sex determination, we identified single population early giving rise to both pre-granulosa potential steroidogenic precursor cells. By comparing XX XY cells, provide evidence gonadal supporting are specified from these by...
The gonad is a unique biological system for studying cell-fate decisions. However, major questions remain regarding the identity of somatic progenitor cells and transcriptional events driving cell differentiation. Using time-series single-cell RNA sequencing on XY mouse gonads during sex determination, we identified single population prior to determination. A subset these progenitors differentiates into Sertoli cells, process characterized by highly dynamic genetic program consisting...
Gonadal sex determination represents a unique model for studying cell fate decisions. However, complete understanding of the different lineages forming developing testis and ovary remains elusive. Here, we investigated origin, specification, subsequent sex-specific differentiation previously uncharacterized population supporting-like cells (SLCs) in mouse gonads. The SLC lineage is closely related to coelomic epithelium specified as early E10.5, making it first somatic be bipotential gonad....
Abstract Despite the importance of germ cell (GC) differentiation for sexual reproduction, gene networks underlying their fate remain unclear. Here, we comprehensively characterize expression dynamics during sex determination based on single‐cell RNA sequencing 14 914 XX and XY mouse GCs between embryonic days (E) 9.0 16.5. We found that diverge transcriptionally as early E11.5 with upregulation genes downstream bone morphogenic protein (BMP) nodal/Activin pathways in GCs, respectively. also...
During embryonic development, mutually antagonistic signaling cascades determine gonadal fate toward a testicular or ovarian identity. Errors in this process result disorders of sex development (DSDs), characterized by discordance between chromosomal, gonadal, and anatomical sex. The absence an appropriate, accessible vitro system is major obstacle understanding mechanisms sex-determination/DSDs. Here, we describe protocols for differentiation mouse human pluripotent cells progenitors....
Sex determination in mammals depends on the differentiation of supporting lineage gonads into Sertoli or pregranulosa cells that govern testis and ovary development, respectively. Although Y-linked testis-determining gene Sry has been identified, ovarian-determining factor remains unknown. In this study, we identified -KTS, a major, alternatively spliced isoform Wilms tumor suppressor WT1, as key determinant female sex determination. Loss -KTS variants blocked gonadal mice, whereas increased...
Mammalian sex determination is controlled by the antagonistic interactions of two genetic pathways: The SRY-SOX9-FGF9 network promotes testis partly opposing proovarian pathways, while RSPO1/WNT-β-catenin/FOXL2 signals control ovary development inhibiting SRY-SOX9-FGF9. molecular basis this mutual antagonism unclear. Here we show that ZNRF3, a WNT signaling antagonist and direct target RSPO1-mediated inhibition, required for in mice. XY mice lacking ZNRF3 exhibit complete or partial gonadal...
Abstract Sertoli cells (SCs), the only somatic within seminiferous tubules, associate intimately with developing germ cells. They not provide physical and nutritional support but also secrete factors essential to complex developmental processes of cell proliferation differentiation. The SC transcriptome must therefore adapt rapidly during different stages spermatogenesis. We report comprehensive genome-wide expression profiles pure populations SCs isolated at 5 distinct first wave mouse...
The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety organ systems. Post-translational covalent attachment cholesterol palmitate Hh are critical for multimerization long range signaling potency. However, the biological impact lipid modifications on ligand distribution signal reception humans remains unclear. In present study, we report unique case autosomal recessive syndromic 46,XY Disorder Sex Development (DSD) with...
Abstract Motivation Recent advances in transcriptomics have enabled unprecedented insight into gene expression analysis at a single-cell resolution. While it is anticipated that the number of publications based on such technologies will increase next decade, there currently no public resource to centralize and enable scientists explore datasets published field reproductive biology. Results Here, we present major update ReproGenomics Viewer, cross-species cross-technology web-based...
Retinoic acid synthesis is not essential for meiosis in fetal ovaries, challenging the dogma about meiosis-inducing factors.
Leydig cells (LC) are the main testicular androgen-producing cells. In eutherian mammals, two types of LCs emerge successively during development, fetal (FLCs) and adult (ALCs). Both display significant differences in androgen production regulation. Using bulk RNA sequencing, we compared transcriptomes both LC populations to characterize their specific transcriptional functional features. Despite similar transcriptomic profiles, a quarter genes show variations expression between FLCs ALCs....
Leydig cells (LCs) are the major androgen-producing in testis. They arise from steroidogenic progenitors (SPs), whose origins, maintenance, and differentiation dynamics remain largely unknown. Single-cell transcriptomics reveal that mouse lineage is specified as early embryonic day 12.5 (E12.5) has a dual mesonephric coelomic origin. SPs specifically express Wnt5a gene evolve rapidly. At E12.5 E13.5, they give rise first to an intermediate population of pre-LCs, finally fetal LCs. E16.5,...
The insulin family of growth factors (insulin, IGF1, and IGF2) are critical in sex determination, adrenal differentiation, testicular function. Notably, the IGF system has been reported to mediate proliferation steroidogenic cells. However, precise role contribution membrane receptors mediating those effects, namely, insülin receptor (INSR) type-I insülin-like factor (IGF1R), have not, oür knowledge, investigated. We show here that specific deletion both Insr Igf1r cells mice leads severe...
During development, motor axons are guided toward muscle target by various extrinsic cues including extracellular matrix (ECM) proteins whose identities and cellular source remain poorly characterized. Here, using single-cell RNAseq of sorted GFP + cells from smyhc1:gfp -injected zebrafish embryos, we unravel the slow progenitors (SMP) pseudotemporal trajectory at level show that differentiating SMPs a major ECM proteins. The SMP core-matrisome was characterized computationally predicted to...
Gonadal sex determination in mice is a complex and dynamic process, which crucial for the development of functional reproductive organs. The expression genes involved this process regulated by variety genetic epigenetic mechanisms. Recently, there has been increasing evidence that transposable elements (TEs), are class mobile elements, play significant role regulating gene during embryogenesis organ development. In study, we aimed to investigate involvement TEs regulation mouse embryonic...
Summary Despite the importance of germ cell (GC) differentiation for sexual reproduction, gene networks underlying their fate remain unclear. Here, we comprehensively characterize expression dynamics during sex determination based on single-cell RNA sequencing 14,914 XX and XY mouse GCs between embryonic days (E) 9.0 16.5. We found that diverge transcriptionally as early E11.5 with upregulation genes downstream Bone morphogenic protein (BMP) Nodal/Activin pathways in GCs, respectively. also...
The effects of PPIs on human sperm fertilizing capacity were poorly investigated although these drugs are widely over-used. Two publications retrospectively studied relationships between any PPI intake and parameters from patients consulting at infertility clinics, but the conclusions reports contradictory. Only two lansoprazole omeprazole motility found to be deleterious neutral for motility. inconsistency effect in previous emphasizes need more basic research spermatozoa, taking into...