Summary of Study ST002072
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 PR001314. The data can be accessed directly via it's Project DOI: 10.21228/M8VT5T 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.
| Study ID | ST002072 |
| Study Title | A non-dividing population with high pyruvate dehydrogenase kinase activity drives metabolic heterogeneity and tumorigenesis in the intestine |
| Study Summary | Although reprogramming of cellular metabolism is a hallmark of cancer, little is known about how metabolic reprogramming contributes to early stages of transformation. Here, we show that the histone deacetylase SIRT6 regulates tumor initiation during intestinal cancer by controlling glucose metabolism. Loss of SIRT6 results in increased number of intestinal stem cells (ISCs), which translates into enhanced tumor initiating potential in APCmin mice. More importantly, we found a metabolic compartmentalization within the intestinal epithelium and adenomas, where a rare population of cells exhibit features of Warburg-like metabolism characterized by high pyruvate dehydrogenase kinase (PDK) activity. Our results show that these cells are quiescent cells expressing +4 ISCs and enteroendocrine markers. Active glycolysis in these cells suppresses ROS accumulation and enhances their stem cell and tumorigenic potential. Our studies reveal that aerobic glycolysis represents a highly heterogeneous feature of cancer, and more importantly, they indicate that this metabolic adaptation occurs in non-dividing cells, suggesting a role for the Warburg effect beyond biomass production in tumors. |
| Institute | Massachusetts General Hospital |
| Department | Brigham and Women's Hospital |
| Last Name | Mostoslavsky |
| First Name | Raul |
| Address | 55 Fruit Street Boston, MA 02114 |
| rmostoslavsky@mgh.harvard.edu | |
| Phone | 5189653364 |
| Submit Date | 2022-01-19 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | imzML |
| Analysis Type Detail | MALDI-MS |
| Release Date | 2022-02-16 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001314 |
| Project DOI: | doi: 10.21228/M8VT5T |
| Project Title: | A non-dividing population with high pyruvate dehydrogenase kinase activity drives metabolic heterogeneity and tumorigenesis in the intestine |
| Project Summary: | Although reprogramming of cellular metabolism is a hallmark of cancer, little is known about how metabolic reprogramming contributes to early stages of transformation. Here, we show that the histone deacetylase SIRT6 regulates tumor initiation during intestinal cancer by controlling glucose metabolism. Loss of SIRT6 results in increased number of intestinal stem cells (ISCs), which translates into enhanced tumor initiating potential in APCmin mice. More importantly, we found a metabolic compartmentalization within the intestinal epithelium and adenomas, where a rare population of cells exhibit features of Warburg-like metabolism characterized by high pyruvate dehydrogenase kinase (PDK) activity. Our results show that these cells are quiescent cells expressing +4 ISCs and enteroendocrine markers. Active glycolysis in these cells suppresses ROS accumulation and enhances their stem cell and tumorigenic potential. Our studies reveal that aerobic glycolysis represents a highly heterogeneous feature of cancer, and more importantly, they indicate that this metabolic adaptation occurs in non-dividing cells, suggesting a role for the Warburg effect beyond biomass production in tumors. |
| Institute: | Massachusetts General Hospital |
| Last Name: | Mostoslavsky |
| First Name: | Raul |
| Address: | 55 Fruit Street Boston, MA 02114 |
| Email: | rmostoslavsky@mgh.harvard.edu |
| Phone: | 617-643-3146 |
Subject:
| Subject ID: | SU002154 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA194782 | adenoma_dan_HCl_3 | adenoma |
| SA194783 | adenoma_dan_HCl_2 | adenoma |
| SA194784 | adenoma_colon_HCl_1 | adenoma |
| Showing results 1 to 3 of 3 |
Collection:
| Collection ID: | CO002147 |
| Collection Summary: | As stated in the paper: Colorectal tissue was stored at -80 °C until processing. Cryosections of the colorectal tissue, containing the adenoma, were taken at 10 µm thickness and were mounted on indium tin oxide (ITO) slides for MALDI MSI analysis. Serial sections were obtained for MALDI MSI and immunofluorescence microscopy using a pPDH antibody and DAPI staining. The cryosections used for immunofluorescence were 5 µm in thickness. Fluorescent microscopy images were acquired using a 40x objective (Zeiss Observer Z.1, Oberkochen, Germany), a DAPI filter (Filter Set 49, Carl Zeiss Microscopy, Oberkochen, Germany), and an FITC filter (31001, Chroma Technology Corporation, Bellows Falls, VT). |
| Sample Type: | Colon |
Treatment:
| Treatment ID: | TR002166 |
| Treatment Summary: | N/A |
Sample Preparation:
| Sampleprep ID: | SP002160 |
| Sampleprep Summary: | As stated in the paper: 4.4 mg/mL of 1,5-diaminonapthalene hydrochloride (CAS: 2243-62-41, Sigma-Aldrich, Darnstadt, Germany) was dissolved in 4/4.5/0.5 HPLC grade water/ethanol/1 M HCl (v/v/v). 28 The 10 µm thick tissue sections were sprayed using a TM-sprayer (HTX Technologies, Chapel Hill, NC) in a four-pass method. The parameters of the matrix application set in the TM-sprayer were as follows: spray nozzle velocity (1200 mm/min), track spacing (2 mm), flow rate (0.09 mL/min), spray nozzle temperature (75 °C), and nitrogen gas pressure (10 psi) |
Combined analysis:
| Analysis ID | AN003377 |
|---|---|
| Analysis type | MS |
| Chromatography type | None (Direct infusion) |
| Chromatography system | timsTOF fleX |
| Column | none |
| MS Type | MALDI |
| MS instrument type | QTOF |
| MS instrument name | Bruker timsTOF fleX |
| Ion Mode | NEGATIVE |
| Units | Da |
Chromatography:
| Chromatography ID: | CH002496 |
| Instrument Name: | timsTOF fleX |
| Column Name: | none |
| Chromatography Type: | None (Direct infusion) |
MS:
| MS ID: | MS003144 |
| Analysis ID: | AN003377 |
| Instrument Name: | Bruker timsTOF fleX |
| Instrument Type: | QTOF |
| MS Type: | MALDI |
| MS Comments: | SCilS 2022a pro |
| Ion Mode: | NEGATIVE |
