A5083926681- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Renal and related cancers
- Microtubule and mitosis dynamics
- Sexual Differentiation and Disorders
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- interferon and immune responses
- Animal Genetics and Reproduction
- Urological Disorders and Treatments
- Ubiquitin and proteasome pathways
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Hormonal Regulation and Hypertension
- Reproductive System and Pregnancy
- Steroid Chemistry and Biochemistry
- Circular RNAs in diseases
- Sex and Gender in Healthcare
- RNA Research and Splicing
- Nuclear Structure and Function
- Testicular diseases and treatments
- Growth Hormone and Insulin-like Growth Factors
- Adrenal Hormones and Disorders
- Wnt/β-catenin signaling in development and cancer
University of Geneva
2018-2025
Université Côte d'Azur
2010-2024
Inserm
2010-2024
Centre National de la Recherche Scientifique
2013-2024
Institut de Biologie Valrose
2013-2024
Centre Hospitalier Universitaire de Grenoble
2024
University of Bayreuth
2023-2024
Yale University
2024
University of California, Los Angeles
2024
Observatoire de la Côte d’Azur
2023
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...
Congenital abnormalities of the kidney and urinary tract are some most common defects detected in unborn child. Kidney growth is controlled by GDNF/RET signalling pathway, but molecular events required for activation RET downstream targets still poorly understood. Here we show that SOX9, a gene involved campomelic dysplasia (CD) humans, together with its close homologue SOX8, plays an essential role signalling. Expression SOX9 can be found from earliest stages renal development within...
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...
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...
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,...
Abstract Gonadal sexual fate in mammals is determined during embryonic development and must be actively maintained adulthood. In the mouse ovary, oestrogen receptors FOXL2 protect ovarian granulosa cells from transdifferentiation into Sertoli cells, their testicular counterpart. However, mechanism underlying protective effect unknown. Here, we show that TRIM28 required to prevent female-to-male sex reversal of ovary after birth. We found upon loss Trim28 , transdifferentiate through an...
Successful testis development relies on the coordinated differentiation and assembly of various cell types to establish both endocrine reproductive functions. The ubiquitin ligase NEDD4 has emerged as a key player in murine development, with this enzyme being implicated gonadal sex determination spermatogonial stem differentiation. Here, we report hitherto uncharacterized roles postnatal development. Utilizing Nr5a1- Amh-Cre drivers conditionally ablate Nedd4 testicular somatic cells, show...
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...
Male infertility is an important health concern that expected to have a major genetic etiology. Although high-throughput sequencing has linked gene defects more than 50% of rare and severe sperm anomalies, less 20% common moderate forms are explained. We hypothesized this low success rate could at least be partly due oligogenic – the accumulation several heterozygous variants in distinct, but functionally connected, genes. Here, we compared fertility parameters male mice harboring one four...
Adrenal cortex and gonads represent the two major steroidogenic organs in mammals. Both tissues are considered to share a common developmental origin characterized by expression of Nr5a1/Sf1. The precise adrenogonadal progenitors processes driving differentiation toward adrenal or gonadal fate remain, however, elusive. Here, we provide comprehensive single-cell transcriptomic atlas early mouse development including 52 cell types belonging twelve lineages. Trajectory reconstruction reveals...
Stem cell-like properties of glioma initiating cells (GiCs) fuel glioblastoma (GBM) development by providing the different cell types that comprise tumor. It is therefore likely molecular circuitries regulate their decision to self-renew or commit a more differentiated state may offer targets for future innovative therapies. In previous micro-RNA profiling studies search regulators stem plasticity, we identified miR-18a* as potential candidate and its expression correlated with stemness...
The IGFs are the major intratesticular factors regulating immature Sertoli cell proliferation and are, therefore, critical to establish magnitude of sperm production. However, source IGF production downstream signaling pathway mediating IGF-dependent remain unclear. Single-cell RNA sequencing on mouse embryonic testis revealed a robust expression Igf1 Igf2 in interstitial steroidogenic progenitors, suggesting that exert paracrine actions cells. To elucidate intracellular mechanism underlies...
From a cohort of 167 infertile patients suffering from multiple morphological abnormalities the flagellum (MMAF), pathogenic bi-allelic mutations were identified in CCDC146 gene. In somatic cells, is located at centrosome and microtubule-related organelles during mitotic division, suggesting that it microtubule-associated protein (MAP). To decipher molecular pathogenesis infertility associated with mutations, Ccdc146 knock-out (KO) mouse line was created. KO male mice infertile, sperm...
WTX/AMER1 is a novel negative regulator of the WNT/beta-catenin pathway with mutations detected in Wilms' tumors and an X-linked sclerosing bone dysplasia. (Fam123b) shares several domains homology two other recently identified proteins: AMER2 (Fam123a) AMER3 (Fam123c). Here, we describe in-depth expression analysis all three members this gene family during mouse embryonic development. All genes were strongly expressed central as well peripheral nervous system, thus suggesting important...
Directed differentiation of pluripotent stem cells into specialized cell types represents an invaluable tool for a wide range applications. Here, we have exploited single-cell transcriptomic data to develop stepwise in vitro system from mouse embryonic adrenocortical cells. We show that during development, the adrenal primordium is embedded extracellular matrix containing tenascin and fibronectin. Culturing on fibronectin increased expression steroidogenic marker NR5A1. Furthermore, 3D...
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...
Abstract 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 (SLC) in mouse gonads. The SLC lineage is closely related to coelomic epithelium specified as early E10.5, making it first somatic be bipotential...
From a cohort of 167 infertile patients suffering from multiple morphological abnormalities the flagellum (MMAF), pathogenic bi-allelic mutations were identified in CCDC146 gene. In somatic cells, is located at centrosome and microtubule-related organelles during mitotic division, suggesting that it microtubule-associated protein (MAP). To decipher molecular pathogenesis infertility associated with mutations, Ccdc146 knock-out (KO) mouse line was created. KO male mice infertile, sperm...
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)
Summary Gonadal sexual fate in mammals is determined during embryonic development and must be actively maintained adulthood. In the mouse ovary, oestrogen receptors FOXL2 protect ovarian granulosa cells from transdifferentiation into Sertoli cells, their testicular counterpart. However, mechanism underlying protective effect unknown. Here, we show that TRIM28 required to prevent female-to-male sex reversal of ovary after birth. We found upon loss Trim28 , transdifferentiate through an...