MassIVE MSV000092457

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GNPS - Metabolic and Proteomic Changes in Sickle Cell Disease and thalassemia Mouse Splenic and Hepatic Macrophages and Peripheral Blood Mononuclear cells

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Description

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 Hbb mice may be relevant to disease to progression in other tissue. [doi:10.25345/C5SF2MN77] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Sickle cell disease, Beta-thalassemia, macrophage, metabolomics, proteomics, polarization, pulmonary hypertension, PBMCs

Contact

Principal Investigators:
(in alphabetical order) 		Angelo D'alessandro, University of Colorado - Anschutz Medical Campus, USA
David Irwin, University of Colorado - Anschutz Medical Campus, United States
Submitting User: mdziecia
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GNPS content goes here (MSV000092457 [task=c3aeb116303c4ca0a1c4ccb46bf4af26])
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