Searching the Resource Information Network

Our searching services are busy right now. Please try again later

  • Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

A Metformin-Responsive Metabolic Pathway Controls Distinct Steps in Gastric Progenitor Fate Decisions and Maturation.

Zhi-Feng Miao | Mahliyah Adkins-Threats | Joseph R Burclaff | Luciana H Osaki | Jing-Xu Sun | Yan Kefalov | Zheng He | Zhen-Ning Wang | Jason C Mills
Cell stem cell | 2020

Cellular metabolism plays important functions in dictating stem cell behaviors, although its role in stomach epithelial homeostasis has not been evaluated in depth. Here, we show that the energy sensor AMP kinase (AMPK) governs gastric epithelial progenitor differentiation. Administering the AMPK activator metformin decreases epithelial progenitor proliferation and increases acid-secreting parietal cells (PCs) in mice and organoids. AMPK activation targets Krüppel-like factor 4 (KLF4), known to govern progenitor proliferation and PC fate choice, and PGC1α, which we show controls PC maturation after their specification. PC-specific deletion of AMPKα or PGC1α causes defective PC maturation, which could not be rescued by metformin. However, metformin treatment still increases KLF4 levels and suppresses progenitor proliferation. Thus, AMPK activates KLF4 in progenitors to reduce self-renewal and promote PC fate, whereas AMPK-PGC1α activation within the PC lineage promotes maturation, providing a potential suggestion for why metformin increases acid secretion and reduces gastric cancer risk in humans.

Pubmed ID: 32243780

Additional research tools detected in this publication

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK094989
  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK077653
  • Agency: NCRR NIH HHS, United States
    Id: S10 RR027552
  • Agency: NIGMS NIH HHS, United States
    Id: R25 GM103757
  • Agency: NCI NIH HHS, United States
    Id: P30 CA091842
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK020579
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK110406
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK052574
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK105129

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


AxioVision Imaging System (tool)

RRID:SCR_002677

Digital image processing system where microscope settings and processing steps may be adjusted in single user interface. Can acquire images from variety of cameras. Includes software package for capturing, archiving and preparing images for publication. Allows users to visualize and present images in several dimensions. Functionality of imaging toolbox expands constantly with wide range of different modules that are tailored to specific applications or microscope accessories. This resource is duplicated by SCR_018376

View all literature mentions

LKB1 (Ley 37D/G6) (antibody)

RRID:AB_627890

This monoclonal targets STK11

View all literature mentions

Phospho-S6 Ribosomal Protein (Ser240/244) Antibody (antibody)

RRID:AB_331682

This polyclonal targets Phospho-S6 Ribosomal Protein (Ser240/244)

View all literature mentions

Cytochrome C antibody [7H8.2C12] (antibody)

RRID:AB_300470

This monoclonal targets Cytochrome C antibody [7H8.2C12]

View all literature mentions

Ki67 antibody - Proliferation Marker (antibody)

RRID:AB_443209

This polyclonal targets Ki67 antibody - Proliferation Marker

View all literature mentions

GFP (B-2) (antibody)

RRID:AB_627695

This monoclonal targets GFP (B-2)

View all literature mentions

Mucin 5AC antibody [45M1] (antibody)

RRID:AB_2146844

This monoclonal targets MUC5AC

View all literature mentions

Gastrin antibody (antibody)

RRID:AB_2108243

This polyclonal targets Gast

View all literature mentions

VEGF-B (C-19) (antibody)

RRID:AB_2213301

This polyclonal targets VEGFB

View all literature mentions

GFP Antibody (FL) (antibody)

RRID:AB_641123

This polyclonal targets GFP

View all literature mentions

Ezrin (3C12) (antibody)

RRID:AB_783303

This monoclonal targets Ezrin (3C12)

View all literature mentions

Anti-Sox9 (antibody)

RRID:AB_2239761

This polyclonal targets Sox9

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

B6N.129(FVB)-Ppargc1atm2.1Brsp/J (organism)

RRID:IMSR_JAX:009666

Mus musculus with name B6N.129(FVB)-Ppargc1atm2.1Brsp/J from IMSR.

View all literature mentions

B6.FVB-Tg(Atp4b-cre)1Jig/JcmiJ (organism)

RRID:IMSR_JAX:030656

Mus musculus with name B6.FVB-Tg(Atp4b-cre)1Jig/JcmiJ from IMSR.

View all literature mentions

STOCK Prkaa1tm1.1Sjm/J (organism)

RRID:IMSR_JAX:014141

Mus musculus with name STOCK Prkaa1tm1.1Sjm/J from IMSR.

View all literature mentions

C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions

B6.129S4(FVB)-Ppargc1atm1Brsp/J (organism)

RRID:IMSR_JAX:008597

Mus musculus with name B6.129S4(FVB)-Ppargc1atm1Brsp/J from IMSR.

View all literature mentions

B6.129(Cg)-Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J (organism)

RRID:IMSR_JAX:007676

Mus musculus with name B6.129(Cg)-Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J from IMSR.

View all literature mentions

Gene Set Enrichment Analysis (software resource)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

View all literature mentions

STOCK Prkaa2tm1.1Sjm/J (organism)

RRID:IMSR_JAX:014142

Mus musculus with name STOCK Prkaa2tm1.1Sjm/J from IMSR.

View all literature mentions

Mouse Genome Informatics: The Gene Ontology Project (data or information resource)

RRID:SCR_006447

This resource is part of the Gene Ontology Consortium which seeks to provide controlled vocabularies for the description of the molecular function, biological process, and cellular component of gene products. These terms are to be used as attributes of gene products by collaborating databases, facilitating uniform queries across them. GO team members at MGI participate in ontology development, outreach, and functional curation of mouse gene products. The GO vocabularies have a hierarchical structure that permits a range of detail from high-level, broadly descriptive terms to very low level, highly specific terms. This broad range is useful both in annotating genes and in searching for gene information using these terms as search criteria. GO terms are defined, allowing all databases to use the terms consistently and properly. GO annotations in the databases additionally include the publication reference which allowed the association to be made and an evidence statement citing how the association was determined.

View all literature mentions

Adobe Photoshop (software resource)

RRID:SCR_014199

Software for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.

View all literature mentions