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| Status |
Public on May 30, 2014 |
| Title |
High-throughput integration of metabolic and transcriptional profiles reveals major metabolic regulators of macrophage polarization |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Macrophages polarize to divergent functional phenotypes depending on their microenvironment in a highly coordinated process of metabolic and transcriptional rewiring that is still poorly understood. We developed an Integrated Metabolomics and Gene Expression (IMAGE) profiling and analysis pipeline and applied it to extensively characterize global metabolic programs of macrophage polarization. IMAGE analysis identified 7 major (novel and known) regulatory modules responsible for metabolic rewiring during polarization, which we validated through extensive carbon and nitrogen labeling experiments. M1-specific modules included: inflammatory variant of the aspartate-arginosuccinate shunt; TCA cycle break at Idh expression accompanied by citrate accumulation and production of itaconate and fatty acid synthesis. In M2 macrophages we discovered significant role of glutamine in polarization, providing nitrogen for UDP-GlcNAc synthesis. Consistently, glutamine deprivation results in significant M2-specific defect in polarization. Our data provide, for the first time, a global view of the integrated transcriptional and metabolic changes that result in M1 and M2 polarization.
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| Overall design |
Bone-marrow derived macrophages were generated from C57BL/6 mice were plated at ~100k cells per well in 96-well plate and stimulated with either Il4 or combination of LPS&IFNg or left unstimulated for 24 h mRNA was derived from lysates using Invitrogen oligo-dT beads
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| Contributor(s) |
Artyomov MN |
| Citation(s) |
25086775 |
| Submission date |
Dec 06, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Maxim N. Artyomov |
| E-mail(s) |
martyomov@pathology.wustl.edu
|
| Organization name |
Washington University in St.Louis
|
| Department |
Immunology&Pathology
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| Street address |
660 S. Euclid Avenue, Campus Box 8118
|
| City |
St.Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA230777 |
| SRA |
SRP033554 |
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