Summary of project PR001159
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 PR001159. The data can be accessed directly via it's Project DOI: 10.21228/M8WH6D This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001159 |
| Project DOI: | doi: 10.21228/M8WH6D |
| Project Title: | Use of Integrated Metabolomics, Transcriptomics, and Signal Protein Profile to Characterize the Effector Function and Associated Metabotype of Polarized Macrophage Phenotypes |
| Project Type: | Systems biology profiling of ex vivo human macrophage polarization |
| Project Summary: | Macrophages (MΦs) display remarkable plasticity and the ability to activate diverse responses to a host of intracellular and external stimuli. Despite extensive characterization of M1 MΦs and a broad set of M2 MΦs, comprehensive characterization of functional phenotype and associated metabotype driving this diverse MΦ activation remains. Herein, we utilized an ex vivo model to produce six MΦ functional phenotypes. Isolated CD14+ PBMCs were differentiated into resting M0 MΦs, and then polarized into M1 (IFN-γ/LPS), M2a (IL-4/IL-13), M2b (IC/LPS), M2c (IL-10), and M2d (IL-6/LIF) MΦs. The MΦs were profiled using a bioanalyte matrix of four cell surface markers, ~50 secreted proteins, ~800 expressed myeloid genes, and ~450 identified metabolites relative to M0 MΦs. Signal protein and expressed gene profiles grouped the MΦs into inflammatory (M1 and M2b) and wound resolution (M2a, M2c, and M2d) phenotypes; however, each had a unique metabolic profile. While both M1 and M2b MΦs shared metabotype profiles consistent with an inflammatory signature; key differences were observed in the TCA cycle, FAO, and OXPHOS. Additionally, M2a, M2c, and M2d MΦs all profiled as tissue repair MΦs; however, metabotype differences were observed in multiple pathways including hexosamine, polyamine, and fatty acid metabolism. These metabolic and other key functional distinctions suggest phagocytic and proliferative functions for M2a MΦs, and angiogenesis and ECM assembly capabilities for M2b, M2c, and M2d MΦs. By integrating metabolomics into a systems analysis of MΦ phenotypes, we provide the most comprehensive map of MΦ diversity to date, along with the global metabolic shifts that correlate to MΦ functional plasticity in these phenotypes. |
| Institute: | Boise VA Medical Center |
| Department: | Research |
| Laboratory: | Ammons |
| Last Name: | Ammons |
| First Name: | Mary Cloud |
| Address: | Mail Stop 151, Bldg 117, 500 W. Fort St. Boise, Idaho 83702 |
| Email: | MaryCloud.AmmonsAnderson@va.gov |
| Phone: | 208-422-1219 |
| Funding Source: | NIGMS |
Summary of all studies in project PR001159
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001835 | Use of Integrated Metabolomics, Transcriptomics, and Signal Protein Profile to Characterize the Effector Function and Associated Metabotype of Polarized Macrophage Phenotypes | Homo sapiens | Idaho Veterans Research and Education Foundation | MS | 2021-09-17 | 1 | 36 | Not available |
