Summary of Study ST002726
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 PR001691. The data can be accessed directly via it's Project DOI: 10.21228/M84B0K 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 | ST002726 |
| Study Title | Metabolic and Proteomic Divergence is Present in Circulating Monocytes and Tissue Resident Macrophages from Berkeley Sickle Cell Anemia and B-thalassemia mice (Spleen) |
| Study Summary | Sickle cell disease and Beta-thalassemia represent hemoglobinopathies arising from dysfunctional or under produced beta-globin chains, respectively. In both diseases, red blood cell injury and anemia are the impetus for end organ injury. Because persistent erythrophagocytosis is a hallmark of these genetic maladies it is critical to understand how macrophage phenotype polarizations in tissue compartments can inform on disease progression. Murine models of sickle cell disease and Beta-thalassemia allow for a basic understanding of mechanisms and provide for translation to human disease. A multi-omics approach to understanding macrophage metabolism and protein changes in two murine models of beta-globinopathy was performed on peripheral blood mononuclear cells as well as spleen and liver macrophages isolated from Berkley sickle cell disease (Berk-ss) and heterozygous B1/B2 globin gene deletion (Hbbth3/+) mice. Results from these experiments revealed the metabolome and proteome of macrophages are polarized to a distinct phenotype in Berk-ss and Hbbth3/+ compared each other and their common background mice (C57BL6/J). Further, spleen and liver macrophages revealed distinct disease specific phenotypes, suggesting macrophages become differentially polarized and reprogrammed within tissue compartments. We conclude that tissue recruitment, polarization, metabolic and proteomic reprogramming of macrophages in Berk-ss and Hbbth3/+ mice may be relevant to disease to progression in other tissue. |
| Institute | University of Colorado School of Medicine |
| Laboratory | Laboratory of Angelo D'Alessandro in collaboratation with David Irwin |
| Last Name | Cendali |
| First Name | Francesca |
| Address | 13199 East Montview Boulevard, Aurora, CO, 80045, USA |
| francesca.cendali@cuanschutz.edu | |
| Phone | 3037246131 |
| Submit Date | 2023-06-05 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-06-20 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO002825 |
| Collection Summary: | The spleen organ tissue were harvested, finely minced, and each organ placed individually in 2mL Eppendorf tubes containing 1mL of DMEM with Collagenase D (Sigma Aldrich, product #11088866001). The tissues were incubated at 37C with agitation for 30 minutes. After incubation, 100 uL of 0.1M EDTA was added to the tissue-containing tubes and placed on ice. A single cell suspension was created by addition of Hanks buffered salt solution (HBSS, Corning, product #MT21022CV), passing through a 100 um filter, and collected in a 15 mL conical tube. The cell suspension was spun at 500g for 5 minutes and the supernatant discarded. The remaining tissue/cell solution was resuspended in 5ml of RBC lysis buffer (Invitrogen eBiosciences, product #00-4333-57), incubated at room temperature for 15 minutes, and centrifuged at 500g for 5 minutes, this step was repeated if RBC presence was sustained. Next, the cells were washed with Miltenyi buffer (HBSS, 0.5M EDTA, Fetal bovine serum), resuspended in 180uL Miltenyi buffer, and incubated on ice with CD11b Microbeads (Miltenyi Biotech, product #130-093-636) for 15minutes. Positive cells were isolated using magnetic LS columns (Miltenyi Biotech, product #130-042-401), collected in 2 mL Eppendorf tubes, counted, and then final pellet aliquots were frozen in liquid nitrogen and stored at -80C. continuously using LabScribe2 and analyzed offline. |
| Sample Type: | Macrophages |
