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dc.contributor.authorLiu, Ying
dc.contributor.authorPop, Ramona
dc.contributor.authorSadegh, Cameron
dc.contributor.authorBrugnara, Carlo
dc.contributor.authorHaase, Volker H.
dc.contributor.authorSocolovsky, Merav
dc.date2022-08-11T08:09:44.000
dc.date.accessioned2022-08-23T16:41:41Z
dc.date.available2022-08-23T16:41:41Z
dc.date.issued2006-03-11
dc.date.submitted2008-04-14
dc.identifier.citationBlood. 2006 Jul 1;108(1):123-33. Epub 2006 Mar 9. <a href="http://dx.doi.org/10.1182/blood-2005-11-4458">Link to article on publisher's site</a>
dc.identifier.issn0006-4971 (Print)
dc.identifier.doi10.1182/blood-2005-11-4458
dc.identifier.pmid16527892
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39933
dc.description.abstractErythropoietin (Epo) is the principal regulator of the erythropoietic response to hypoxic stress, through its receptor, EpoR. The EpoR signals mediating the stress response are largely unknown, and the spectrum of progenitors that are stress responsive is not fully defined. Here, we used flow cytometry to identify stress-responsive Ter119+CD71highFSChigh early erythroblast subsets in vivo. In the mouse spleen, an erythropoietic reserve organ, early erythroblasts were present at lower frequencies and were undergoing higher rates of apoptosis than equivalent cells in bone marrow. A high proportion of splenic early erythroblasts coexpressed the death receptor Fas, and its ligand, FasL. Fas-positive early erythroblasts were significantly more likely to coexpress annexin V than equivalent, Fas-negative cells, suggesting that Fas mediates early erythroblast apoptosis in vivo. We examined several mouse models of erythropoietic stress, including erythrocytosis and beta-thalassemia. We found a dramatic increase in the frequency of splenic early erythroblasts that correlated with down-regulation of Fas and FasL from their cell surface. Further, a single injection of Epo specifically suppressed early erythroblast Fas and FasL mRNA and cell-surface expression. Therefore, Fas and FasL are negative regulators of erythropoiesis. Epo-mediated suppression of erythroblast Fas and FasL is a novel stress response pathway that facilitates erythroblast expansion in vivo.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16527892&dopt=Abstract">Link to article in PubMed</a>
dc.subjectAnimals
dc.subjectAntigens, CD95
dc.subjectCell Survival
dc.subjectDisease Models, Animal
dc.subjectDown-Regulation
dc.subjectErythroblasts
dc.subjectErythropoiesis
dc.subjectErythropoietin
dc.subjectFas Ligand Protein
dc.subjectFlow Cytometry
dc.subjectGene Expression Profiling
dc.subjectGene Expression Regulation
dc.subjectMice
dc.subjectMice, Inbred BALB C
dc.subjectMice, Inbred C57BL
dc.subjectMice, Inbred MRL lpr
dc.subjectMice, Transgenic
dc.subjectRNA, Messenger
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleSuppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo
dc.typeJournal Article
dc.source.journaltitleBlood
dc.source.volume108
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1273&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/274
dc.identifier.contextkey489611
refterms.dateFOA2022-08-23T16:41:41Z
html.description.abstract<p>Erythropoietin (Epo) is the principal regulator of the erythropoietic response to hypoxic stress, through its receptor, EpoR. The EpoR signals mediating the stress response are largely unknown, and the spectrum of progenitors that are stress responsive is not fully defined. Here, we used flow cytometry to identify stress-responsive Ter119+CD71highFSChigh early erythroblast subsets in vivo. In the mouse spleen, an erythropoietic reserve organ, early erythroblasts were present at lower frequencies and were undergoing higher rates of apoptosis than equivalent cells in bone marrow. A high proportion of splenic early erythroblasts coexpressed the death receptor Fas, and its ligand, FasL. Fas-positive early erythroblasts were significantly more likely to coexpress annexin V than equivalent, Fas-negative cells, suggesting that Fas mediates early erythroblast apoptosis in vivo. We examined several mouse models of erythropoietic stress, including erythrocytosis and beta-thalassemia. We found a dramatic increase in the frequency of splenic early erythroblasts that correlated with down-regulation of Fas and FasL from their cell surface. Further, a single injection of Epo specifically suppressed early erythroblast Fas and FasL mRNA and cell-surface expression. Therefore, Fas and FasL are negative regulators of erythropoiesis. Epo-mediated suppression of erythroblast Fas and FasL is a novel stress response pathway that facilitates erythroblast expansion in vivo.</p>
dc.identifier.submissionpathoapubs/274
dc.contributor.departmentDepartment of Pediatrics
dc.source.pages123-33


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