Evidence map›Paper›PMID 24759943›Full record

ArticlePloS one2014

Quantitative-proteomic comparison of alpha and Beta cells to uncover novel targets for lineage reprogramming.

Amit Choudhary, Kaihui Hu He, Philipp Mertins, Namrata D Udeshi, Vlado Dančík, Dina Fomina-Yadlin, Stefan Kubicek, Paul A Clemons, Stuart L Schreiber, Steven A Carr and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. The Ca(2+)/Calmodulin/CaMKK2 Axis: Nature's Metabolic CaMshaft.Trends in endocrinology and metabolism: TEM · 2016
    Review
  7. Article
  8. Article
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

11 authors at 2 institutions in 1 country.

Amit ChoudharySociety of Fellows, Harvard University, Cambridge, Massachusetts, United States of America; Center for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts, United States of America.
Kaihui Hu HeCenter for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts, United States of America.
Philipp MertinsCenter for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts, United States of America.
Namrata D UdeshiCenter for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts, United States of America.
Vlado DančíkCenter for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts, United States of America.
Dina Fomina-YadlinCenter for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts, United States of America; Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, United States of America.
Stefan KubicekCenter for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts, United States of America.
Paul A ClemonsCenter for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts, United States of America.
Stuart L SchreiberCenter for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts, United States of America; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.
Steven A CarrCenter for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts, United States of America.
Bridget K WagnerCenter for the Science of Therapeutics, Broad Institute, Cambridge, Massachusetts, United States of America.
Broad Institute · USHarvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Type-1 diabetes (T1D) is an autoimmune disease in which insulin-secreting pancreatic beta cells are destroyed by the immune system. An emerging strategy to regenerate beta-cell mass is through transdifferentiation of pancreatic alpha cells to beta cells. We previously reported two small molecules, BRD7389 and GW8510, that induce insulin expression in a mouse alpha cell line and provide a glimpse into potential intermediate cell states in beta-cell reprogramming from alpha cells. These small-molecule studies suggested that inhibition of kinases in particular may induce the expression of several beta-cell markers in alpha cells. To identify potential lineage reprogramming protein targets, we compared the transcriptome, proteome, and phosphoproteome of alpha cells, beta cells, and compound-treated alpha cells. Our phosphoproteomic analysis indicated that two kinases, BRSK1 and CAMKK2, exhibit decreased phosphorylation in beta cells compared to alpha cells, and in compound-treated alpha cells compared to DMSO-treated alpha cells. Knock-down of these kinases in alpha cells resulted in expression of key beta-cell markers. These results provide evidence that perturbation of the kinome may be important for lineage reprogramming of alpha cells to beta cells.

Indexed as

AnimalsCalcium-Calmodulin-Dependent Protein Kinase KinaseCell LineGlucagon-Secreting CellsInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsMicePhosphorylationProtein Serine-Threonine KinasesProteomicsBRSK1 protein, humanCalcium-Calmodulin-Dependent Protein Kinase KinaseCamkk2 protein, mouseIntracellular Signaling Peptides and ProteinsProtein Serine-Threonine Kinases

Identifiers

PMID24759943
PMCPMC3997365
OpenAlexW2094526048

What OpenQuestion holds

Textmetadata
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.