ArticleThe Journal of clinical investigation2015
Differentiation of hypothalamic-like neurons from human pluripotent stem cells.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 131 citations in OpenAlex.
- Scalable hypothalamic neuron differentiation from human pluripotent stem cells suitable for modeling metabolic disorders.Stem cell reports · 2026Article
- Generation of human appetite-regulating neurons and tanycytes from pluripotent stem cells.Cell stem cell · 2026Article
- The plant hormone, 6-benzylaminopurine, ameliorates obesity in male and female mice while on a high-fat diet.Molecular metabolism · 2026Article
- From identity to function: unveiling the cellular complexity of hypothalamic feeding circuits.Reviews in endocrine & metabolic disorders · 2026Review
- NGF administration is associated with increased GnRH immunoreactivity and a GnRH-associated phenotype in hypothalamic NSCs of aging mice.Frontiers in endocrinology · 2026Article
- The accessory protein MRAP2 directly interacts with melanocortin-3 receptor to enhance signaling.Science signaling · 2025Article
- Control of aging-associated neurodegeneration via hypothalamic extracellular vesicles containing parathymosin.Cell reports · 2025Article
- An optimized method for directed differentiation of hypothalamic neural stem cells in a 3D culture system.Scientific reports · 2025Article
- Control of tuberal hypothalamic development and its implications in metabolic disorders.Nature reviews. Endocrinology · 2025Review
- Article
- Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of FAIM2.Cell genomics · 2024Article
- Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR ofbioRxiv : the preprint server for biology · 2023Article
- Differentiation, Transcriptomic Profiling, and Calcium Imaging of Human Hypothalamic Neurons.Current protocols · 2023Article
- MKRN3 inhibits puberty onset via interaction with IGF2BP1 and regulation of hypothalamic plasticity.JCI insight · 2023Article
- Generation of hypothalamic neural stem cell-like cells in vitro from human pluripotent stem cells.Stem cell reports · 2023Article
- A neuroepithelial wave of BMP signalling drives anteroposterior specification of the tuberal hypothalamus.eLife · 2023Article
- Article
- Adult neurogenesis of the median eminence contributes to structural reconstruction and recovery of body fluid metabolism in hypothalamic self-repair after pituitary stalk lesion.Cellular and molecular life sciences : CMLS · 2022Article
- Human organoids in basic research and clinical applications.Signal transduction and targeted therapy · 2022Review
- NPFF Decreases Activity of Human Arcuate NPY Neurons: A Study in Embryonic-Stem-Cell-Derived Model.International journal of molecular sciences · 2022Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
The hypothalamus is the central regulator of systemic energy homeostasis, and its dysfunction can result in extreme body weight alterations. Insights into the complex cellular physiology of this region are critical to the understanding of obesity pathogenesis; however, human hypothalamic cells are largely inaccessible for direct study. Here, we developed a protocol for efficient generation of hypothalamic neurons from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) obtained from patients with monogenetic forms of obesity. Combined early activation of sonic hedgehog signaling followed by timed NOTCH inhibition in human ESCs/iPSCs resulted in efficient conversion into hypothalamic NKX2.1+ precursors. Application of a NOTCH inhibitor and brain-derived neurotrophic factor (BDNF) further directed the cells into arcuate nucleus hypothalamic-like neurons that express hypothalamic neuron markers proopiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AGRP), somatostatin, and dopamine. These hypothalamic-like neurons accounted for over 90% of differentiated cells and exhibited transcriptional profiles defined by a hypothalamic-specific gene expression signature that lacked pituitary markers. Importantly, these cells displayed hypothalamic neuron characteristics, including production and secretion of neuropeptides and increased p-AKT and p-STAT3 in response to insulin and leptin. Our results suggest that these hypothalamic-like neurons have potential for further investigation of the neurophysiology of body weight regulation and evaluation of therapeutic targets for obesity.
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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.