Summary of Study ST002119

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001344. The data can be accessed directly via it's Project DOI: 10.21228/M80D9F This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002119
Study TitleMetabolomics analysis of zebrafish response to CID661578 treatment
Study Summaryzebrafish larvae were treated with DMSO or CID661578 for 24 hours prior to global metabolomics analysis (n=6). Metabolites were extracted from pools of 10 zebrafish larvae at 5 dpf using a 80% methanol-based extraction method. Samples were dried in speed vac and stored in -80C freezer until ready for LC-MS analysis.
Institute
North Carolina State University
Last NameLiu
First NameXiaojing
AddressPolk Hall, RM 128
Emailxliu68@ncsu.edu
Phone9195154387
Submit Date2022-03-30
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2022-04-14
Release Version1
Xiaojing Liu Xiaojing Liu
https://dx.doi.org/10.21228/M80D9F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001344
Project DOI:doi: 10.21228/M80D9F
Project Title:MNK2 deficiency potentiates beta-cell regeneration via hypertranslation
Project Summary:Regenerating pancreatic beta-cells is a potential curative approach for diabetes. We previously identified the small molecule CID661578 as a potent inducer of beta-cell regeneration but its target and mechanism of action have remained unknown. We now screened 257 million yeast clones and determined that CID661578 targets MAP kinase-interacting serine/threonine kinase 2 (MNK2), an interaction we genetically validated in vivo. CID661578 increased beta-cell neogenesis from ductal cells in zebrafish, neonatal pig islet aggregates and human pancreatic ductal organoids. Mechanistically, we found that CID661578 boosts protein synthesis and regeneration by blocking MNK2 from binding eIF4G in the translation initiation complex at the mRNA cap. Unexpectedly, this blocking activity augmented eIF4E-phosphorylation depending on MNK1 and bolstered the interaction between eIF4E and eIF4G, which is necessary for both hypertranslation and beta-cell regeneration. Taken together, our findings demonstrate a targetable role of MNK2-controlled translation in beta-cell regeneration, a role that warrants further investigation in diabetes.
Institute:North Carolina State University
Last Name:Liu
First Name:Xiaojing
Address:Polk Hall, RM 128
Email:xliu68@ncsu.edu
Phone:9195154387

Subject:

Subject ID:SU002204
Subject Type:Fish
Subject Species:Danio rerio
Taxonomy ID:7955

Factors:

Subject type: Fish; Subject species: Danio rerio (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA203968CID6_PosCID661578
SA203969CID5_PosCID661578
SA203970CID3_PosCID661578
SA203971CID1_NegCID661578
SA203972CID4_PosCID661578
SA203973CID3_NegCID661578
SA203974CID6_NegCID661578
SA203975CID5_NegCID661578
SA203976CID4_NegCID661578
SA203977CID2_PosCID661578
SA203978CID2_NegCID661578
SA203979CID1_PosCID661578
SA203980CID5CID661578
SA203981CID4CID661578
SA203982CID3CID661578
SA203983CID2CID661578
SA203984CID6CID661578
SA203985CID1CID661578
SA203986DMSO2Control
SA203987DMSO6_NegControl
SA203988DMSO5_NegControl
SA203989DMSO3Control
SA203990DMSO4Control
SA203991DMSO6Control
SA203992DMSO5Control
SA203993DMSO4_NegControl
SA203994DMSO1_NegControl
SA203995DMSO5_PosControl
SA203996DMSO4_PosControl
SA203997DMSO3_PosControl
SA203998DMSO6_PosControl
SA203999DMSO1Control
SA204000DMSO2_NegControl
SA204001DMSO2_PosControl
SA204002DMSO1_PosControl
SA204003DMSO3_NegControl
Showing results 1 to 36 of 36

Collection:

Collection ID:CO002197
Collection Summary:zebrafish larvae were treated with DMSO or CID661578 for 24 hours prior to global metabolomics analysis (n=6). Metabolites were extracted from pools of 10 zebrafish larvae at 5 dpf using a 80% methanol/water-based extraction method. Detailed metabolite extraction was described previously using 80% methanol/water as solvent (PMID: 24410464, PMID: 24894601, PMID: 25795660) and dry pellets were stored in -80 °C freezer until ready for LC-MS analysis. Pellets were reconstituted into 30 μL of sample solvent (water:methanol:acetonitrile, 2:1:1, v/v), and 5 μL was injected into the LC-MS.
Sample Type:new

Treatment:

Treatment ID:TR002216
Treatment Summary:Chemicals (DMSO orCID661578) were added to the E3 medium for larvae to reach final concentration of 10 uM. Pools of 10 wild-type (WT) larvae at 5 dpf were used for each of the 6 independent biological replicates for DMSO or CID661578 treatment from 4-5 dpf.

Sample Preparation:

Sampleprep ID:SP002210
Sampleprep Summary:Intracellular metabolites were harvested as described previously using 80% methanol/water as solvent (PMID: 24410464, PMID: 24894601, PMID: 25795660) and dry pellets were stored in -80 °C freezer until ready for LC-MS analysis. For metabolite analysis, pellets were reconstituted into 30 μL of sample solvent (water:methanol:acetonitrile, 2:1:1, v/v), and 5 μL was injected into the LC-MS.

Combined analysis:

Analysis ID AN003467 AN003468 AN003469 AN003470
Analysis type MS MS MS MS
Chromatography type HILIC HILIC HILIC HILIC
Chromatography system Thermo Dionex Ultimate 3000 Thermo Dionex Ultimate 3000 Thermo Dionex Ultimate 3000 Thermo Dionex Ultimate 3000
Column Waters Xbridge amide (100 x 2.1mm,3.5um) Waters Xbridge amide (100 x 2.1mm,3.5um) Waters Xbridge amide (100 x 2.1mm,3.5um) Waters Xbridge amide (100 x 2.1mm,3.5um)
MS Type ESI ESI ESI ESI
MS instrument type Orbitrap Orbitrap Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Plus Orbitrap Thermo Q Exactive Plus Orbitrap Thermo Q Exactive Plus Orbitrap Thermo Q Exactive Plus Orbitrap
Ion Mode POSITIVE NEGATIVE POSITIVE NEGATIVE
Units ion counts ion counts ion counts ion counts

Chromatography:

Chromatography ID:CH002561
Chromatography Summary:HILIC method is for general metabolomics analysis.
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:Waters Xbridge amide (100 x 2.1mm,3.5um)
Chromatography Type:HILIC

MS:

MS ID:MS003228
Analysis ID:AN003467
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:It was operated in the full-scan mode (positive/negative switching) with the resolution set at 70 000 (at m/z 200).LC-MS data were analyzed using Sieve 2.0 (Thermo Scientific), and the integrated area under metabolite peak was used to compare the relative abundance of each metabolite in different samples in the same batch.
Ion Mode:POSITIVE
  
MS ID:MS003229
Analysis ID:AN003468
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:It was operated in the full-scan mode (positive/negative switching) with the resolution set at 70 000 (at m/z 200).LC-MS data were analyzed using Sieve 2.0 (Thermo Scientific), and the integrated area under metabolite peak was used to compare the relative abundance of each metabolite in different samples in the same batch.
Ion Mode:NEGATIVE
  
MS ID:MS003230
Analysis ID:AN003469
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:It was operated in the full-scan mode (positive ion mode only) with the resolution set at 70 000 (at m/z 200).LC-MS data were analyzed using Sieve 2.0 (Thermo Scientific), and the integrated area under metabolite peak was used to compare the relative abundance of each metabolite in different samples in the same batch.
Ion Mode:POSITIVE
  
MS ID:MS003231
Analysis ID:AN003470
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:It was operated in the full-scan mode (negative ion mode only) with the resolution set at 70 000 (at m/z 200).LC-MS data were analyzed using Sieve 2.0 (Thermo Scientific), and the integrated area under metabolite peak was used to compare the relative abundance of each metabolite in different samples in the same batch.
Ion Mode:NEGATIVE
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