Expression data of immortlized GnRH neuron cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE174902 | GEO | 2023/02/28
REPOSITORIES: GEO
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Project description:During development, gonadotropin releasing hormone (GnRH) neurons are born in the nasal placode and migrate to the hypothalamus, where they position to regulate sexual reproduction. Defective GnRH neuron development may lead to GnRH deficiency (GD) which is characterized by absent or delayed puberty. Several GD causative genes have been identified so far, but half of the cases are still idiopathic. The identification of candidate genes is also hampered by the difficulty in isolating and studying GnRH neurons, which are small in number, develop in a short developmental window and lack specific markers. Gene expression profiles of GnRH neurons are lacking, as obtaining primary GnRH neurons is challenging and no reports on gene expression profiles during the whole developmental process of GnRH neurons are available. In this work, we obtained the transcriptomic profile of sorted GFP-positive and unsorted GFP-negative cells from Gnrh1-GFP rat embryos at three developmental stages, representing the initiation (embryonic day (E)14), the peak (E17) and the completion of GnRH neuronal migration (E20).
2023-02-28 | GSE174896 | GEO
Project description:We used microarrays to detail the global program of gene expression underlying gonadotropin-releasing hormone (GnRH) generation and delamination from the olfactory placode.
2016-09-30 | GSE87486 | GEO
Project description:During embryonic development, the olfactory placode (OP) gives rise to various populations of neurons; these include putative olfactory pioneer neurons, different neurons of unknown identity and function, cells of the terminal nerve, and the Gonadotropin-releasing hormone-1 (GnRH-1) neurons. In mice, the GnRH-1 neurons are first detectable in the developing olfactory system around mid-gestation. From here, the GnRH-1 neurons migrate, along the axons of the terminal nerve (TN), to various regions of the developing brain. Once in the brain, the GnRH-1 neurons play a central role in controlling the hypothalamic-pituitary-gonadal (HPG) axis. Early migratory neurons forming from the olfactory placode have been proposed to play a vital role in inducing olfactory bulb morphogenesis. Kallmann syndrome is a condition characterized by defective development of the olfactory system and infertility. Murine studies have demonstrated the critical role of the Prokineticin 2-Prokinteicin Receptor 2 pathway in olfactory bulb morphogenesis and GnRH-1 neuronal migration. Loss-of-function Prokr2 mutations cause both Kallmann syndrome associated with bulb agenesis and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). Following Prokr2 expression and lineage tracing, we found that Prokr2 is not expressed by the cells of the developing olfactory bulb but by migratory putative pioneer/terminal nerve neurons. Performing single-cell-RNA-sequencing, we identified genes enriched in the migratory cells of the putative terminal nerve. By integrating genetic lineage tracing and single-cell transcriptomics, we identified previously undescribed populations of migratory neurons that appear to be enriched in the expression of several genes related to olfactory defects, GnRH migratory deficiencies and infertility.
2024-03-11 | GSE234871 | GEO
Project description:Analysis of GT1-7 cells treated with GnRH. In this dataset, we include the expression data obtained from GT1-7 cells after treatment with GnRH. We confirmed that GT1-7 cells expressed DUSP5 and DUSP6 after GnRH treatment. Results provide insight into the effect of GnRH on MAP kinase pathway.
2018-05-31 | GSE112857 | GEO
Project description:Fertility critically depends on the gonadotropin-releasing hormone (GnRH) pulse generator, a neural construct comprised of hypothalamic neurons coexpressing kisspeptin, neurokoinin-B and dynorphin. Here, using mathematical modeling and in vivo optogenetics we reveal for the first time how this neural construct initiates and sustains the appropriate ultradian frequency essential for reproduction. Prompted by mathematical modeling, we show experimentally using female estrous mice that robust pulsatile release of luteinizing hormone, a proxy for GnRH, emerges abruptly as we increase the basal activity of the neuronal network using continuous low-frequency optogenetic stimulation. Further increase in basal activity markedly increases pulse frequency and eventually leads to pulse termination. Additional model predictions that pulsatile dynamics emerge from nonlinear positive and negative feedback interactions mediated through neurokinin-B and dynorphin signaling respectively are confirmed neuropharmacologically. Our results shed light on the long-elusive GnRH pulse generator offering new horizons for reproductive health and wellbeing.SIGNIFICANCE STATEMENT The gonadotropin-releasing hormone (GnRH) pulse generator controls the pulsatile secretion of the gonadotropic hormones LH and FSH and is critical for fertility. The hypothalamic arcuate kisspeptin neurons are thought to represent the GnRH pulse generator, since their oscillatory activity is coincident with LH pulses in the blood; a proxy for GnRH pulses. However, the mechanisms underlying GnRH pulse generation remain elusive. We developed a mathematical model of the kisspeptin neuronal network and confirmed its predictions experimentally, showing how LH secretion is frequency-modulated as we increase the basal activity of the arcuate kisspeptin neurons in vivo using continuous optogenetic stimulation. Our model provides a quantitative framework for understanding the reproductive neuroendocrine system and opens new horizons for fertility regulation
Model is encoded by Johannes and submitted to BioModels by Ahmad Zyoud.
2024-09-02 | BIOMD0000000931 | BioModels
Project description:Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are central regulators of fertility and integrate endogenous hormonal status with environmental cues to ensure reproductive success. Here, we found that extra-hypothalamic GnRH neurons in the olfactory bulb of adult mice and humans (GnRHOB) can mediate social recognition. We show that GnRHOB neurons extend neurites into the vomeronasal organ and olfactory epithelium and project to the hypothalamic median eminence. We demonstrate that male GnRHOB neurons express vomeronasal and olfactory receptors, are activated by female odors in vivo, and mediate gonadotropin release in response to female urine. We find that male preference for female odors is enhanced upon chemogenetic activation of GnRHOB neurons and is impaired after genetic inhibition or ablation of these cells and relies on GnRH signaling in the posterodorsal medial amygdala. Taken together, these results establish GnRHOB neurons as a central regulatory hub regulating fertility, sex recognition, and mating in males.
2024-06-17 | GSE268138 | GEO
Project description:Hypothalamic gonadotropin-releasing hormone (GnRH) neurons lays the foundation for human development and reproduction, however, the critical cell populations and the entangled mechanisms underlying the development of human GnRH neurons remain poorly understood. Here, by utilizing our established human pluripotent stem cells-derived GnRH neuron model, we decoded the cellular heterogeneity and differentiation trajectories at the single-cell level. We found that a glutamatergic neuron population, which generated together with GnRH neurons, showed similar transcriptomic properties with olfactory sensory neuron and provided the migratory path for GnRH neurons. Through trajectory analysis, we identified a specific gene module activated along the GnRH neuron differentiation lineage, and we examined one of the transcription factors, DLX5, expression in human fetal GnRH neurons. Furthermore, we found that Wnt inhibition could increase DLX5 expression, and improve the GnRH neuron differentiation efficiency through promoting neurogenesis and switching the differentiation fates of neural progenitors into glutamatergic neurons/GnRH neurons. Our research comprehensively reveals the dynamic cell population transition and gene regulatory network during GnRH neuron differentiation.
2022-10-04 | GSE212901 | GEO
Project description:Polycystic ovary syndrome (PCOS) is the most common form of infertility in women. The causes of PCOS are not yet understood and both genetics and early-life exposure have been considered as candidates. With regard to the latter, circulating androgens are elevated in mid-late gestation in women with PCOS, potentially exposing offspring to elevated androgens in utero; daughters of women with PCOS are at increased risk for developing this disorder. Consistent with these clinical observations, prenatal androgenization (PNA) of several species recapitulates many phenotypes observed in PCOS. There is increasing evidence that symptoms associated with PCOS, including elevated luteinizing hormone (LH) (and presumably gonadotropin-releasing hormone (GnRH)) pulse frequency emerge during the pubertal transition. We utilized translating ribosomal affinity purification coupled with RNA sequencing to examine GnRH neuron mRNAs from prepubertal (3wk) and adult female control and PNA mice. Prominent in GnRH neurons were transcripts associated with protein synthesis and cellular energetics, in particular oxidative phosphorylation. The GnRH neuron transcript profile was affected more by the transition from prepuberty to adulthood than by PNA treatment, however PNA did change the developmental trajectory of GnRH neurons. This included families of transcripts related to both protein synthesis and oxidative phosphorylation, which were more prevalent in adults than in prepubertal mice but were blunted in PNA adults. These findings suggest that prenatal androgen exposure can program alterations in the translatome of GnRH neurons, providing a mechanism independent of changes in the genetic code for altered expression.
2020-10-13 | GSE155314 | GEO
Project description:Reproduction requires pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH), which regulates expression of the pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Fshb expression shows an inverted U-shaped response to GnRH pulse frequency. Increasing GnRH pulse frequency beyond ~one pulse/2 hours, despite increasing the average GnRH concentration, induces progressively less Fshb. To clarify regulatory mechanisms underlying Fshb gene control, we developed three biologically inspired and topologically distinct mathematical models. The models represent: 1) parallel activation of Fshb inhibitory and stimulatory factors (e.g. inhibin α, VGF), 2) activation of a signaling component with a refractory period (e.g. G protein), and 3) inactivation of a factor needed for Fshb induction (e.g. GDF9). Simulations with all three models recapitulated the Fshb expression levels obtained in standard perifusion experiments at different GnRH pulse frequencies. Notably, simulations altering average concentration, pulse duration and frequency showed that the apparent frequency-dependent pattern of Fshb expression obtained with model 1 actually resulted from variations in average GnRH concentration. In contrast, models 2 and 3 showed “true” frequency sensing. To resolve which components of this GnRH signal induce Fshb, a massively parallel experimental system was developed. Analysis of over 4000 samples in ~40 experiments indicated that, while early genes Egr1 and Fos respond only to variations in GnRH concentration, Fshb induction is sensitive to GnRH pulse frequency changes, whilst maintaining the same average concentration. These results provide a framework for understanding the role of different regulatory factors in modulating the responses of the Fshb gene.
2017-04-07 | GSE86119 | GEO
Project description:Reproduction requires pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH), which regulates expression of the pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Fshb expression shows an inverted U-shaped response to GnRH pulse frequency. Increasing GnRH pulse frequency beyond ~one pulse/2 hours, despite increasing the average GnRH concentration, induces progressively less Fshb. To clarify regulatory mechanisms underlying Fshb gene control, we developed three biologically inspired and topologically distinct mathematical models. The models represent: 1) parallel activation of Fshb inhibitory and stimulatory factors (e.g. inhibin α, VGF), 2) activation of a signaling component with a refractory period (e.g. G protein), and 3) inactivation of a factor needed for Fshb induction (e.g. GDF9). Simulations with all three models recapitulated the Fshb expression levels obtained in standard perifusion experiments at different GnRH pulse frequencies. Notably, simulations altering average concentration, pulse duration and frequency showed that the apparent frequency-dependent pattern of Fshb expression obtained with model 1 actually resulted from variations in average GnRH concentration. In contrast, models 2 and 3 showed “true” frequency sensing. To resolve which components of this GnRH signal induce Fshb, a massively parallel experimental system was developed. Analysis of over 4000 samples in ~40 experiments indicated that, while early genes Egr1 and Fos respond only to variations in GnRH concentration, Fshb induction is sensitive to GnRH pulse frequency changes, whilst maintaining the same average concentration. These results provide a framework for understanding the role of different regulatory factors in modulating the responses of the Fshb gene.
2017-04-07 | GSE86123 | GEO