Evidence map›Paper›PMID 33667549›Full record

ArticleThe Journal of biological chemistry

Defective insulin receptor signaling in hPSCs skews pluripotency and negatively perturbs neural differentiation.

Adrian Kee Keong Teo, Linh Nguyen, Manoj K Gupta, Hwee Hui Lau, Larry Sai Weng Loo, Nicholas Jackson, Chang Siang Lim, William Mallard, Marina A Gritsenko, John L Rinn and 3 more

Abstract read
In one paragraph

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. 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

13 authors.

Adrian Kee Keong TeoSection of Islet Cell and Regenerative Biology, Department of Medicine, Joslin Diabetes Center, Brigham and Women's Hospital, Harvard Medical School, and Harvard Stem Cell Institute, Boston, Massachusetts, USA; Stem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, Proteos, Singapore, Singapore; Department of Biochemistry and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address: drainteo@gmail.com.
Linh NguyenStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, Proteos, Singapore, Singapore; Department of Biochemistry and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Manoj K GuptaSection of Islet Cell and Regenerative Biology, Department of Medicine, Joslin Diabetes Center, Brigham and Women's Hospital, Harvard Medical School, and Harvard Stem Cell Institute, Boston, Massachusetts, USA.
Hwee Hui LauStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, Proteos, Singapore, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
Larry Sai Weng LooStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, Proteos, Singapore, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
Nicholas JacksonSection of Islet Cell and Regenerative Biology, Department of Medicine, Joslin Diabetes Center, Brigham and Women's Hospital, Harvard Medical School, and Harvard Stem Cell Institute, Boston, Massachusetts, USA.
Chang Siang LimStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, Proteos, Singapore, Singapore.
William MallardDepartment of Stem Cell and Regenerative Biology, Harvard University, and Broad Institute of MIT, Cambridge, Massachusetts, USA.
Marina A GritsenkoBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
John L RinnDepartment of Stem Cell and Regenerative Biology, Harvard University, and Broad Institute of MIT, Cambridge, Massachusetts, USA.
Richard D SmithBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Wei-Jun QianBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Rohit N KulkarniSection of Islet Cell and Regenerative Biology, Department of Medicine, Joslin Diabetes Center, Brigham and Women's Hospital, Harvard Medical School, and Harvard Stem Cell Institute, Boston, Massachusetts, USA. Electronic address: rohit.kulkarni@joslin.harvard.edu.

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Equipment Supplement Request for a Research Resource for Ultra-sensitive High Throughput ProteomicsP41GM103493 · NIGMS · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI SMITH, RICHARD D · 2012 to 2022
$22.6M
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
Interrogation of dynamic RNA modifications in beta cells in type 1 diabetesUC4DK116278 · NIDDK · JOSLIN DIABETES CENTER · PI HE, CHUAN, KULKARNI, ROHIT N. · 2017 to 2017
$1.9M
NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK067536NIDDK NIH HHS R01 DK103215NIDDK NIH HHS UC4 DK116278NIGMS NIH HHS P41 GM103493
6 · The paper itself

Abstract

Human embryonic stem cells are a type of pluripotent stem cells (hPSCs) that are used to investigate their differentiation into diverse mature cell types for molecular studies. The mechanisms underlying insulin receptor (IR)-mediated signaling in the maintenance of human pluripotent stem cell (hPSC) identity and cell fate specification are not fully understood. Here, we used two independent shRNAs to stably knock down IRs in two hPSC lines that represent pluripotent stem cells and explored the consequences on expression of key proteins in pathways linked to proliferation and differentiation. We consistently observed lowered pAKT in contrast to increased pERK1/2 and a concordant elevation in pluripotency gene expression. ERK2 chromatin immunoprecipitation, luciferase assays, and ERK1/2 inhibitors established direct causality between ERK1/2 and OCT4 expression. Of importance, RNA sequencing analyses indicated a dysregulation of genes involved in cell differentiation and organismal development. Mass spectrometry-based proteomic analyses further confirmed a global downregulation of extracellular matrix proteins. Subsequent differentiation toward the neural lineage reflected alterations in SOX1

Indexed as

Cell DifferentiationCell LineCells, CulturedHuman Embryonic Stem CellsHumansMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NeuronsOctamer Transcription Factor-3PhosphorylationPluripotent Stem CellsProteomicsReceptor, InsulinSignal TransductionMAPK1 protein, humanMAPK3 protein, humanMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Octamer Transcription Factor-3POU5F1 protein, humanReceptor, InsulinAKTcell fate specificationdifferentiationERK1/2humaninsulin receptorsneural lineagepluripotencysignalingstem cells

Identifiers

PMID33667549
PMCPMC8050001

What OpenQuestion holds

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LicenceCC BY
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.