ArticleCell stem cell2018
Super-Obese Patient-Derived iPSC Hypothalamic Neurons Exhibit Obesogenic Signatures and Hormone Responses.
Article in Cell stem cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- 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
- Dual SMAD inhibition as a versatile platform in human pluripotent stem cell-based regenerative medicine and disease modeling.Molecules and cells · 2025Review
- Cardiometabolic disease and cardio-oncology: Insights from iPSC models and tissue engineering.Cell reports. Medicine · 2025Review
- IGF1 Signaling Regulates Neuropeptide Expression in Hypothalamic Neurons Under Physiological and Pathological Conditions.Endocrinology · 2025Article
- Control of tuberal hypothalamic development and its implications in metabolic disorders.Nature reviews. Endocrinology · 2025Review
- Anti-obesity compounds, Semaglutide and LiPR, and PrRP do not change the proportion of human and mouse POMC+ neurons.PloS one · 2025Article
- 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
- Organoids in endocrine and metabolic research: current and emerging applications.Nature reviews. Endocrinology · 2024Article
- Neuron stress-related genes serve as new biomarkers in hypothalamic tissue following high fat diet.Frontiers in endocrinology · 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
- Proteomics of novel induced pluripotent stem cell-derived vascular endothelial cells reveal extensive similarity with an immortalized human endothelial cell line.Physiological genomics · 2023Article
- Current Treatments for Patients with Genetic ObesityJournal of clinical research in pediatric endocrinology · 2023Review
- Article
- The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits.Nature reviews. Endocrinology · 2022Review
- Developmental modeling of hepatogenesis using obese iPSCs-hepatocyte differentiation uncovers pathological features.Cell death & disease · 2022Article
- NPFF Decreases Activity of Human Arcuate NPY Neurons: A Study in Embryonic-Stem-Cell-Derived Model.International journal of molecular sciences · 2022Article
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Abstract
The hypothalamus contains neurons that integrate hunger and satiety endocrine signals from the periphery and are implicated in the pathophysiology of obesity. The limited availability of human hypothalamic neurons hampers our understanding of obesity disease mechanisms. To address this, we generated human induced pluripotent stem cells (hiPSCs) from multiple normal body mass index (BMI; BMI ≤ 25) subjects and super-obese (OBS) donors (BMI ≥ 50) with polygenic coding variants in obesity-associated genes. We developed a method to reliably differentiate hiPSCs into hypothalamic-like neurons (iHTNs) capable of secreting orexigenic and anorexigenic neuropeptides. Transcriptomic profiling revealed that, although iHTNs maintain a fetal identity, they respond appropriately to metabolic hormones ghrelin and leptin. Notably, OBS iHTNs retained disease signatures and phenotypes of high BMI, exhibiting dysregulated respiratory function, ghrelin-leptin signaling, axonal guidance, glutamate receptors, and endoplasmic reticulum (ER) stress pathways. Thus, human iHTNs provide a powerful platform to study obesity and gene-environment interactions.
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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.