FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1514366758> ?p ?o ?g. }

• W1514366758 abstract "Transforming Growth Factor beta (TGFβ) signaling plays an important role in a variety of cellular processes during embryonic development, adult tissue homeostasis and cancer. TGFβI ligand is a potent inhibitor of early hematopoietic progenitor [1] cells in vitro, however the exact role and mechanisms of this pathway during adult hematopoietic homeostasis remains poorly understood. The Transcriptional Intermediary Factor 1 gamma (Tif1γ) gene encodes a recently uncovered nuclear protein in the TGFβ transduction pathway. Tif1γ is defective in the zebrafish moonshine mutant, which exhibits primitive and definitive hematopoiesis defects [2]. In addition, Tif1γ has been shown to influence differentiation of human erythroid cells in vitro [3]. Recent work in our laboratory has provided genetic evidence that Tif1γ is required for the generation and survival of hematopoietic stem/progenitor cells during murine development (C.Adolphe, K.Shakhbazov et al., manuscript under submission). Given that Tif1γ function is required for embryonic development and null mutants are embryonic lethal [4] (R.Losson unpublished data), we took advantage of a conditional Tif1γ flox allele (R.Losson unpublished data) and combined it with the inducible MxCre line [5] to generate mice in which Tif1γ function can be specifically ablated during adult hematopoiesis. MxCre:Tif1γKO/flox mutants exhibit a decrease in erythroblasts and dramatic increase in granulocytes within the bone marrow. This phenotype is attributable to a massive increase in granulocyte-monocyte progenitors (GMPs) at the expense of common myeloid progenitors (CMPs) and megakaryocyte- erythrocyte progenitors (MEPs), which are severely decreased in Tif1γ mutant bone marrow. In addition, pre-B cells were dramatically decreased in numbers, attributable to an increase in cell death, indicating a pro-survival role for Tif1γ in B lymphocytes. In addition, we performed deletion of Tif1γ in non-competitive and competitive bone marrow transplantation settings, which indicated that only the CMP/MEP phenotype is a non-cell autonomous effect. Two distinct models have been reported suggesting how Tif1γ functions within the TGFβ pathway: one indicating that Tif1γ binds and acts through Smad2/3 and the other that Tif1γ functions as a Smad4 mono-ubiquitin ligase [3, 6, 7]. To genetically address this apparent discrepancy, we generated double Tif1γ/Smad4 hematopoietic specific mutant mice, whose phenotype was surprisingly similar to that observed in Tif1γ single mutants. These data suggest that Tif1γ function is independent of Smad4 in hematopoietic cells. To address the mechanism by which Tif1γ functions, we performed microarray profiling of normal and mutant progenitors, which revealed prostaglandin D2 synthase as a hub gene linking Tif1γ and TGFβ signaling. Finally, we were able to mimic the hematopoietic-Tif1γ null phenotype by providing 16,16-dimethyl prostaglandin D2 to wild-type hematopoietic cells in vitro. In summary, our data provide genetic evidence for a key role of Tif1γ during early myeloid development as well as pre-B cell survival. In addition, we have identified that the majority of Tif1γ function is Smad4 independent. Finally, we identified a novel link between Tif1γ function and prostaglandin metabolism/signaling as a likely mechanism by which Tif1γ regulates hematopoiesis." @default.
• W1514366758 created "2016-06-24" @default.
• W1514366758 creator A5058010466 @default.
• W1514366758 date "2009-01-01" @default.
• W1514366758 modified "2023-09-23" @default.
• W1514366758 title "The role of TIF1 gamma during adult murine hematopoiesis" @default.
• W1514366758 doi "https://doi.org/10.5075/epfl-thesis-4415" @default.
• W1514366758 hasPublicationYear "2009" @default.
• W1514366758 type Work @default.
• W1514366758 sameAs 1514366758 @default.
• W1514366758 citedByCount "0" @default.
• W1514366758 crossrefType "journal-article" @default.
• W1514366758 hasAuthorship W1514366758A5058010466 @default.
• W1514366758 hasConcept C104317684 @default.
• W1514366758 hasConcept C109159458 @default.
• W1514366758 hasConcept C145103041 @default.
• W1514366758 hasConcept C201750760 @default.
• W1514366758 hasConcept C203014093 @default.
• W1514366758 hasConcept C2776878037 @default.
• W1514366758 hasConcept C2780007613 @default.
• W1514366758 hasConcept C28328180 @default.
• W1514366758 hasConcept C54355233 @default.
• W1514366758 hasConcept C86803240 @default.
• W1514366758 hasConcept C95444343 @default.
• W1514366758 hasConceptScore W1514366758C104317684 @default.
• W1514366758 hasConceptScore W1514366758C109159458 @default.
• W1514366758 hasConceptScore W1514366758C145103041 @default.
• W1514366758 hasConceptScore W1514366758C201750760 @default.
• W1514366758 hasConceptScore W1514366758C203014093 @default.
• W1514366758 hasConceptScore W1514366758C2776878037 @default.
• W1514366758 hasConceptScore W1514366758C2780007613 @default.
• W1514366758 hasConceptScore W1514366758C28328180 @default.
• W1514366758 hasConceptScore W1514366758C54355233 @default.
• W1514366758 hasConceptScore W1514366758C86803240 @default.
• W1514366758 hasConceptScore W1514366758C95444343 @default.
• W1514366758 hasLocation W15143667581 @default.
• W1514366758 hasOpenAccess W1514366758 @default.
• W1514366758 hasPrimaryLocation W15143667581 @default.
• W1514366758 hasRelatedWork W115156472 @default.
• W1514366758 hasRelatedWork W1891156149 @default.
• W1514366758 hasRelatedWork W1894029484 @default.
• W1514366758 hasRelatedWork W1971806750 @default.
• W1514366758 hasRelatedWork W1974721375 @default.
• W1514366758 hasRelatedWork W1997739317 @default.
• W1514366758 hasRelatedWork W2010385132 @default.
• W1514366758 hasRelatedWork W2067159310 @default.
• W1514366758 hasRelatedWork W2086664962 @default.
• W1514366758 hasRelatedWork W2097567926 @default.
• W1514366758 hasRelatedWork W2109677100 @default.
• W1514366758 hasRelatedWork W2121266842 @default.
• W1514366758 hasRelatedWork W2132341258 @default.
• W1514366758 hasRelatedWork W2151874942 @default.
• W1514366758 hasRelatedWork W2589193943 @default.
• W1514366758 hasRelatedWork W2980304352 @default.
• W1514366758 hasRelatedWork W2996913209 @default.
• W1514366758 hasRelatedWork W766893721 @default.
• W1514366758 hasRelatedWork W1874300226 @default.
• W1514366758 hasRelatedWork W2594724787 @default.
• W1514366758 isParatext "false" @default.
• W1514366758 isRetracted "false" @default.
• W1514366758 magId "1514366758" @default.
• W1514366758 workType "article" @default.