Abstract
Acute anemia initiates a systemic response that results in the rapid mobilization and differentiation of erythroid progenitors in the adult spleen. The flexed-tail (f) mutant mice exhibit normal steady-state erythropoiesis but are unable to rapidly respond to acute erythropoietic stress. Here, we show that f/f mutant mice have a mutation in Madh5. Our analysis shows that BMP4/Madh5-dependent signaling, regulated by hypoxia, initiates the differentiation and expansion of erythroid progenitors in the spleen. These findings suggest a new model where stress erythroid progenitors, resident in the spleen, are poised to respond to changes in the microenvironment induced by acute anemia.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acute Disease
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Alleles
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Anemia / pathology
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Anemia / physiopathology*
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Animals
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / metabolism*
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Cell Differentiation / physiology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Erythroid Cells / cytology*
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Erythroid Cells / metabolism
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Erythropoiesis / physiology*
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Signal Transduction / physiology
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Smad5 Protein
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Spleen / cytology
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Trans-Activators / genetics
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Trans-Activators / metabolism*
Substances
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Bmp4 protein, mouse
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins
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DNA-Binding Proteins
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Phosphoproteins
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Smad5 Protein
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Smad5 protein, mouse
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Trans-Activators