Evidence map›Paper›PMID 33125875›Full record

ArticleStem cell reports2020

Leptin Receptor Signaling Regulates Protein Synthesis Pathways and Neuronal Differentiation in Pluripotent Stem Cells.

Manoj K Gupta, Heidrun Vethe, Samir Softic, Tata Nageswara Rao, Vilas Wagh, Jun Shirakawa, Harald Barsnes, Marc Vaudel, Tomozumi Takatani, Sevim Kahraman and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2020. 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
0.2field-weighted citation impact, top 49% of its field
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, 4 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 3 countries.

Manoj K GuptaSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Heidrun VetheSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA; KG Jebsen Center for Diabetes Research, Department of Clinical Medicine, University of Bergen, Bergen 5009, Norway.
Samir SofticDepartment of Gastroenterology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02215, USA; Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Tata Nageswara RaoSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA; University Clinic of Hematology, Department of Biomedical Research, Inselspital Bern and University of Bern, Bern, Switzerland.
Vilas WaghCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Jun ShirakawaSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Harald BarsnesKG Jebsen Center for Diabetes Research, Department of Clinical Medicine, University of Bergen, Bergen 5009, Norway; Proteomics Unit, Department of Biomedicine, University of Bergen, Norway.
Marc VaudelKG Jebsen Center for Diabetes Research, Department of Clinical Medicine, University of Bergen, Bergen 5009, Norway; Proteomics Unit, Department of Biomedicine, University of Bergen, Norway.
Tomozumi TakataniSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Sevim KahramanSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Masaji SakaguchiSection of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Rachael MartinezSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Jiang HuSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Yngvild BjørlykkeKG Jebsen Center for Diabetes Research, Department of Clinical Medicine, University of Bergen, Bergen 5009, Norway; Department of Pediatrics, Haukeland University Hospital, N-5021 Bergen, Norway.
Helge RaederKG Jebsen Center for Diabetes Research, Department of Clinical Medicine, University of Bergen, Bergen 5009, Norway; Department of Pediatrics, Haukeland University Hospital, N-5021 Bergen, Norway.
Rohit N KulkarniSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: rohit.kulkarni@joslin.harvard.edu.
Harvard University · USJoslin Diabetes Center · USUniversity of Bergen · NOHarvard Stem Cell Institute · USHaukeland University Hospital · NOMassachusetts General Hospital · US

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Pediatric Scientist Development Program (PSDP) [K12]K12HD000850 · NICHD · YALE UNIVERSITY · PI Sallie R. Permar · 1987 to 2026
$44.1M
ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Elizabeth Austen Lawson, Takara Leah Stanley · 1994 to 2026
$31.6M
Role of IGF-1 and Insulin Receptors Beta-Cell SurvivalR01DK067536 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 2004 to 2026
$8.0M
Role of SerpinB1 in beta cell growthR01DK103215 · NIDDK · JOSLIN DIABETES CENTER · PI KULKARNI, ROHIT N. · 2014 to 2018
$2.6M
NICHD NIH HHS K12 HD000850NIDDK NIH HHS P30 DK036836NIDDK NIH HHS P30 DK040561NIDDK NIH HHS R01 DK067536NIDDK NIH HHS R01 DK103215
6 · The paper itself

Abstract

The role of leptin receptor (OB-R) signaling in linking pluripotency with growth and development and the consequences of dysfunctional leptin signaling on progression of metabolic disease is poorly understood. Using a global unbiased proteomics approach we report that embryonic fibroblasts (MEFs) carrying the db/db mutation exhibit metabolic abnormalities, while their reprogrammed induced pluripotent stem cells (iPSCs) show altered expression of proteins involved in embryonic development. An upregulation in expression of eukaryotic translation initiation factor 4e (Eif4e) and Stat3 binding to the Eif4e promoter was supported by enhanced protein synthesis in mutant iPSCs. Directed differentiation of db/db iPSCs toward the neuronal lineage showed defects. Gene editing to correct the point mutation in db/db iPSCs using CRISPR-Cas9, restored expression of neuronal markers and protein synthesis while reversing the metabolic defects. These data imply a direct role for OB-R in regulating metabolism in embryonic fibroblasts and key developmental pathways in iPSCs.

Indexed as

Protein BiosynthesisSignal TransductionAnimalsCell DifferentiationCell LineageCRISPR-Cas SystemsEukaryotic Initiation Factor-4EFibroblastsGene EditingGene Expression Regulation, DevelopmentalInduced Pluripotent Stem CellsMetabolomeMiceMice, KnockoutNeurogenesisProteinseIF4E protein, mouseEukaryotic Initiation Factor-4EProteinsReceptors, LeptinStat3 protein, mouseSTAT3 Transcription FactorcancerdiabetesEIF4Eembryonic developmentleptin receptorneuronal lineagepluripotencySTAT3

Identifiers

PMID33125875
PMCPMC7664055
OpenAlexW3095476580

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.