Summary of project PR002067
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 PR002067. The data can be accessed directly via it's Project DOI: 10.21228/M8F82F This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002067 |
| Project DOI: | doi: 10.21228/M8F82F |
| Project Title: | Trained immunity in hematopoietic stem cell-derived macrophages is defined by a distinct metabolic and epigenetic state |
| Project Summary: | In the present study, we investigate the contribution of long-term hematopoietic stem cells (HSCLT) to trained immunity (TI) in the setting of chronic autoimmune disease. Using a mouse model of systemic lupus erythematosus (SLE), we show that bone marrow derived macrophages (BMDMs) from autoimmune mice exhibit hallmark features of TI, including increased Mycobacterium avium killing and inflammatory cytokine production. Furthermore, these functional properties are mechanistically linked to increased glycolytic metabolism in BMDMs from primary autoimmune mice. While we find that HSC from autoimmune mice constitute a transplantable, long-term reservoir for macrophages that exhibit the functional properties of TI, these BMDMs exhibit a distinctive metabolic state typified by attenuated glycolytic activity. Furthermore, and in contrast to BMDMs from primary autoimmune mice, BMDMs and myeloid progenitors derived from autoimmune donor HSC exhibit a unique pattern of molecular remodeling characterized by reduced chromatin accessibility at a broad array of metabolic genes, while retaining elevated expression of TI-associated transcriptional regulators such as Jun and Fos. Taken together, our data show that HSC exposed to autoimmune inflammation gives rise to macrophages in which the hallmark functional properties of TI are decoupled from glycolytic metabolism. Altogether, our data support a model in which TI is characterized by a spectrum of distinct molecular and metabolic states capable of driving augmented immune function. |
| Institute: | University of Colorado Anschutz Medical Campus |
| Last Name: | Bevers |
| First Name: | Shaun |
| Address: | 12801 E 17th Ave Bldg. RC-1S Rm L2400 Aurora CO 80045 |
| Email: | shaun.bevers@cuanschutz.edu |
| Phone: | 970-217-3413 |
Summary of all studies in project PR002067
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003323 | Global Metabolomics and U-13C6-Glucose Tracing in Bone Marrow Derived Macrophages (BMDM) | Mus musculus | University of Colorado Anschutz Medical Campus | MS | 2024-08-05 | 1 | 60 | Uploaded data (850.6M)* |
