ArticleReproductive biology and endocrinology : RB&E2026
In vitro differentiation of the hypothalamic KNDy neuron, a master regulator for reproduction, from mouse embryonic stem cells.
Article in Reproductive biology and endocrinology : RB&E, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Correction: In vitro differentiation of the hypothalamic KNDy neuron, a master regulator for reproduction, from mouse embryonic stem cells.Reproductive biology and endocrinology : RB&E · 2026Article
Corrections and comments
- Erratum issued
Authors and funding
18 authors.
Funding
Abstract
backgroundHypothalamic kisspeptin neurons are master regulators of reproduction in mammals, including humans and rodents, via direct stimulation of gonadotropin-releasing hormone (GnRH) neurons. Therefore, they play a central role in puberty onset and gonadal function in mammals. Arcuate kisspeptin neurons express both neurokinin B (NKB) and dynorphin A (Dyn). Thus, these neurons are also referred to as KNDy neurons, and accumulating evidence suggests that KNDy neurons are responsible for tonic GnRH/gonadotropin release and the consequent folliculogenesis/steroidogenesis. Notably, mutations in genes encoding kisspeptin (KISS1), kisspeptin receptor (GPR54), or NKB (TAC3) in humans, or deletion of these genes in rodents, cause hypogonadotropic hypogonadism. Therefore, cellular models of KNDy neurons are useful for elucidating the pathogenesis of reproductive disorders and for developing novel therapies for these disorders. Here, we established a method to differentiate KNDy neurons from mouse embryonic stem cells (mESCs).
methodsmESCs were incubated in culture medium containing agents that enhance Sonic Hedgehog signaling, a ventralizing signal, to induce the differentiation of ventral hypothalamic organoids. Kisspeptin-expressing cells were generated by adding a Notch inhibitor, dispersing the aggregates, and transferring them into a two-dimensional culture system. Kisspeptin-, NKB-, and Dyn-expressing cells were identified by immunohistochemistry, and kisspeptin secretion into the culture medium was quantified by enzyme-linked immunosorbent assay.
resultsImmunoreactivity for kisspeptin, NKB, and Dyn was detected in differentiated organoids derived from mESCs. Furthermore, kisspeptin secretion was evident in culture supernatants of differentiated KNDy neurons.
conclusionsThis is the first report demonstrating the differentiation of KNDy neurons from pluripotent stem cells, which can be applied to create cellular models for various diseases caused by KNDy peptide deficiency and may contribute to the development of novel therapeutic approaches and understanding cellular mechanisms regulating mammalian reproduction.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.