ArticleEndocrinology2021
Physiological Characterization and Transcriptomic Properties of GnRH Neurons Derived From Human Stem Cells.
Article in Endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Combined HS6ST1 and HS6ST2 loss disrupts the formation and migration of gonadotropin-releasing hormone neurons.Development (Cambridge, England) · 2026Article
- NGF administration is associated with increased GnRH immunoreactivity and a GnRH-associated phenotype in hypothalamic NSCs of aging mice.Frontiers in endocrinology · 2026Article
- Transcriptomic profiling of murine GnRH neurons reveals developmental trajectories linked to human reproduction and infertility.Theranostics · 2025Article
- Deletion in RMST lncRNA impairs hypothalamic neuronal development in a human stem cell-based model of Kallmann Syndrome.Cell death discovery · 2024Article
- Autism-linked NLGN3 is a key regulator of gonadotropin-releasing hormone deficiency.Disease models & mechanisms · 2023Article
- Polycystic ovary syndrome: pathophysiology and therapeutic opportunities.BMJ medicine · 2023Review
- The initiation and maintenance of gonadotropin-releasing hormone neuron identity in congenital hypogonadotropic hypogonadism.Frontiers in endocrinology · 2023Review
- FGF8-FGFR1 signaling regulates human GnRH neuron differentiation in a time- and dose-dependent manner.Disease models & mechanisms · 2022Article
- The mechanism underlying the pubertal increase in pulsatile GnRH release in primates.Journal of neuroendocrinology · 2022Review
- Epigenetics of functional hypothalamic amenorrhea.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus play a key role in the regulation of reproductive function. In this study, we sought an efficient method for generating GnRH neurons from human embryonic and induced pluripotent stem cells (hESC and hiPSC, respectively). First, we found that exposure of primitive neuroepithelial cells, rather than neuroprogenitor cells, to fibroblast growth factor 8 (FGF8), was more effective in generating GnRH neurons. Second, addition of kisspeptin to FGF8 further increased the efficiency rates of GnRH neurogeneration. Third, we generated a fluorescent marker mCherry labeled human embryonic GnRH cell line (mCh-hESC) using a CRISPR-Cas9 targeting approach. Fourth, we examined physiological characteristics of GnRH (mCh-hESC) neurons: similar to GnRH neurons in vivo, they released the GnRH peptide in a pulsatile manner at ~60 min intervals; GnRH release increased in response to high potassium, kisspeptin, estradiol, and neurokinin B challenges; and injection of depolarizing current induced action potentials. Finally, we characterized developmental changes in transcriptomes of GnRH neurons using hESC, hiPSC, and mCh-hESC. The developmental pattern of transcriptomes was remarkably similar among the 3 cell lines. Collectively, human stem cell-derived GnRH neurons will be an important tool for establishing disease models to understand diseases, such as idiopathic hypothalamic hypogonadism, and testing contraceptive drugs.
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Registered trials
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