A5114376688- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Microtubule and mitosis dynamics
- Adipose Tissue and Metabolism
- Sexual Differentiation and Disorders
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Phytoestrogen effects and research
- MicroRNA in disease regulation
- interferon and immune responses
- Renal and related cancers
- Muscle metabolism and nutrition
- Cancer-related molecular mechanisms research
- Circadian rhythm and melatonin
- Regulation of Appetite and Obesity
- Nuclear Structure and Function
- Muscle Physiology and Disorders
- Reproductive System and Pregnancy
- Adipokines, Inflammation, and Metabolic Diseases
- RNA Interference and Gene Delivery
- Stress Responses and Cortisol
- Metabolism, Diabetes, and Cancer
- Exercise and Physiological Responses
- Receptor Mechanisms and Signaling
University of Geneva
2007-2024
Yale University
2024
Centre Hospitalier Universitaire de Grenoble
2024
University of Bayreuth
2023-2024
University of California, Los Angeles
2024
National Institute of Neurological Disorders and Stroke
1991
National Institutes of Health
1991
National Institute on Alcohol Abuse and Alcoholism
1991
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...
Clones encoding an atypical &adrenergic receptor were isolated from a rat brown adipose tissue cDNA library.This expressed in Chinese hamster ovary (CHO) cells displays low affinity for @-adrenergic antagonists and high BRL 37344, agonist that selectively stimulates lipolysis tissue.The rank order of potency agonistmediated increases intracellular cAMP transfected correlates with agonist-mediated stimulation adipocytes.Northern blot analysis demonstrates this subtype is only white where it...
A new member of the uncoupling protein (UCP) family called UCP3 has recently been cloned and shown to be highly expressed in skeletal muscle rodents humans. In present study, was overexpressed C2C12 myoblasts where it acts as an protein. Changes mRNA expression were examined rodent muscles under conditions known modulate thermogenesis brown adipose tissue. muscle, did not change response 48 h cold exposure (6 degrees C), whereas decreased by 81% or increased 5.6-fold 1 week 50% food...
OBJECTIVE— Emerging evidence suggests that dietary phytoestrogens can have beneficial effects on obesity and diabetes, although their mode of action is not known. Here, we investigate the mechanisms mediating lipid glucose metabolism in rodents. RESEARCH DESIGN AND METHODS— Male CD-1 mice were fed from conception to adulthood with either a high soy–containing diet or soy-free diet. Serum levels circulating isoflavones, ghrelin, leptin, free fatty acids, triglycerides, cholesterol quantified....
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....
Obesity is an increasingly prevalent health problem, and natural effective therapeutic approaches are required to prevent its occurrence. Phytoestrogens plant-derived compounds with estrogenic activities; they can bind both estrogen receptors alpha beta mimic the action of estrogens on target organs.The purpose this study was examine influence soy-derived phytoestrogens energy balance metabolism.Male outbred mice (CD-1) were allowed ad libitum access either a high soy-containing diet or...
Sertoli cells (SCs) are the central, essential coordinators of spermatogenesis, without which germ cell development cannot occur. We previously showed that Dicer, an RNaseIII endonuclease required for microRNA (miRNA) biogenesis, is absolutely to mature, survive, and ultimately sustain development. Here, using isotope-coded protein labeling, a technique relative quantification by mass spectrometry, we investigated impact cell-Dicer subsequent miRNA loss on testicular proteome. found that,...
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...
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....
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...
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...
Uncoupling protein‐3 (UCP3) is a mitochondrial inner‐membrane protein abundantly expressed in rodent and human skeletal muscle which may be involved energy dissipation. Many studies have been performed on the metabolic regulation of UCP3 mRNA level, but little known about expression at level. Two populations mitochondria described muscle, subsarcolemmal (SS) intermyofibrillar (IMF), differ their intracellular localization possibly also role. To examine if differentially these two different...
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...
We and others have previously shown that triple knockout mice lacking the β1/β2/β3-adrenoceptors (β-less mice) developed a progressive obesity at adulthood. Here, we studied glucose homeostasis in β-less before onset of obesity. show increased fat mass are intolerant. In addition, observed impaired glucose-induced insulin secretion exhibit an increase liver PEPCK gene expression fed state, suggesting they gluconeogenesis. Although these characteristics usually associated with resistance,...
UCP3 is a mitochondrial membrane transporter that postulated to uncouple oxidative phosphorylation from ATP synthesis producing heat instead of ATP. Human mainly expressed in skeletal muscle, which plays an important role energy homeostasis and substrate oxidation. Therefore, good candidate gene for obesity. We analyzed, among 734 subjects the Québec Family Study, new GA repeat microsatellite located intervening sequence (IVS) 6 (GAIVS6) gene, two already described restriction fragment...
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...
Summary 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 scRNA-seq XX XY cells, demonstrate supporting emerge from with...
Genetic mutations are a recurrent cause of male infertility. Multiple morphological abnormalities the flagellum (MMAF) syndrome is heterogeneous genetic disease, with which more than 50 genes have been linked. Nevertheless, for 50% patients this condition, no identified. From study cohort 167 MMAF patients, pathogenic bi-allelic were identified in CCDC146 gene two patients. This encodes poorly characterized centrosomal protein we studied detail here. First, localization was cell lines. We...
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...
Abstract Genetic mutations are a recurrent cause of male infertility. Multiple morphological abnormalities the flagellum (MMAF) syndrome is heterogeneous genetic disease, with which more than 50 genes have been linked. Nevertheless, for 50% patients this condition, no identified. From study cohort 167 MMAF patients, pathogenic bi-allelic were identified in CCDC146 gene two patients. This encodes poorly characterized centrosomal protein we studied detail here. First, localization was cell...
Genetic mutations are a recurrent cause of male infertility. Multiple morphological abnormalities the flagellum (MMAF) syndrome is heterogeneous genetic disease, with which more than 50 genes have been linked. Nevertheless, for 50% patients this condition, no identified. From study cohort 167 MMAF patients, pathogenic bi-allelic were identified in CCDC146 gene two patients. This encodes poorly characterized centrosomal protein we studied detail here. First, localization was cell lines. We...