Evidence map›Paper›PMID 42276059›Full record

ArticleStem cell reports2026

Scalable hypothalamic neuron differentiation from human pluripotent stem cells suitable for modeling metabolic disorders.

Vukasin M Jovanovic, Narisu Narisu, Lori L Bonnycastle, David Castellano, Seungmi Ryu, Ravi Tharakan, Kendall T Mesch, Qiang Chen, Fahrünisa Meryem Betül Erol, Hannah J Glover and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors.

Vukasin M JovanovicNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA. Electronic address: vukasin.jovanovic@nih.gov.
Narisu NarisuCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Lori L BonnycastleCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
David CastellanoNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Seungmi RyuNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Ravi TharakanNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Kendall T MeschNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Qiang ChenNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Fahrünisa Meryem Betül ErolNaomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Hannah J GloverNaomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Tingfen YanCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Neelam SinhaCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Chaitali SenNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Shu YangNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Dvir BlivisNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Daniel F BennettDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD, USA.
Giovanni Rosales-SotoDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD, USA.
Jason InmanNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Pinar OrmanogluNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Christopher A LeClairNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Natalie D ShawClinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Menghang XiaNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Martin SchneiderDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD, USA.
Erick O Hernandez-OchoaDepartment of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD, USA.
Michael R ErdosCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Anton SimeonovNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA.
Shuibing ChenDepartment of Surgery, Center for Genomic Health, Weill Cornell Medicine, New York, NY 10065, USA.
Francis S CollinsCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Claudia A DoegeNaomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Carlos A TristanNational Center for Advancing Translational Sciences (NCATS), Division of Preclinical Innovation Rockville, Rockville, MD 20850, USA. Electronic address: carlos.tristan@nih.gov.

Funding

RESEARCH TRAININGP30DK026687 · NIDDK · ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS · PI Anthony W Ferrante, DYMPNA GALLAGHER · 1986 to 2026
$33.0M
The molecular genetic analysis of human obesityR01DK052431 · NIDDK · ROCKEFELLER UNIVERSITY · PI CHUNG, WENDY K, LEIBEL, RUDOLPH L · 1996 to 2020
$11.6M
GENETIC ANALYSIS OF TYPE II DIABETES IN FINNISH POPULATIONZ01HG000024 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI COLLINS, FRANCIS S. · 1995 to 2008
$6.2M
Intramural NIH HHS Z01 HG000024NIDDK NIH HHS P30 DK026687NIDDK NIH HHS R01 DK052431
6 · The paper itself

Abstract

The hypothalamus, composed of multiple nuclei, is essential for maintaining the body's homeostasis. Within the mediobasal hypothalamus, the arcuate nucleus (ARC) contains key neuronal populations, including appetite-suppressing pro-opiomelanocortin (POMC) neurons that regulate energy and glucose balance. Here, we present a chemically defined, scalable method for differentiating human pluripotent stem cells (hPSCs) into hypothalamic neurons enriched for POMC cells, compatible with robotic cell culture platforms for high-throughput use. Neuronal identity was validated by MERFISH single-cell transcriptomics, RNA-Seq, ATAC-Seq, and comparison to human hypothalamus. The method is robust across multiple hPSC lines, showing consistent induction of ventral diencephalon and hypothalamic markers. Derived neurons display metabolic disease-relevant features, including body mass index (BMI)-associated gene enrichment, and ATAC-Seq identifies potential candidate regulatory regions linked to hypothalamic development and metabolic traits. Functional assays reveal neuronal responses to insulin and the GLP-1 receptor agonist Exendin-4, and transcriptional responses to altered glucose conditions. This platform delivers a physiologically relevant model of human hypothalamic neurons that enables deeper mechanistic and therapeutic studies of metabolic disease.

Indexed as

Cell DifferentiationHypothalamusMetabolic DiseasesModels, BiologicalNeuronsPluripotent Stem CellsGlucoseHumansInsulinPro-OpiomelanocortinGlucoseInsulinPro-Opiomelanocortinautomated biomanufacturingGLP1R agonistGnRH neuronshuman hypothalamusinsuliniPSCmetabolic disease modelingobesitypluripotent stem cellsPOMC neuronstype 2 diabetes

Identifiers

PMID42276059
PMCPMC13385436

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.