title: Trim33/Tif1γ is involved in late stages of granulomonopoiesis in mice.
abstract: Trim33/Tif1γ (Trim33) is a member of the tripartite motif family. Using a conditional hematopoietic-specific Trim33 knock-out (Trim33(Δ/Δ)) mouse, we showed previously that Trim33 deficiency in hematopoietic stem cells leads to severe defects in hematopoiesis, resembling the main features of human chronic myelomonocytic leukemia. We also demonstrated that Trim33 is involved in hematopoietic aging through TGFβ signaling. Nevertheless, how Trim33 contributes to the terminal stages of myeloid differentiation remains to be clarified. We reveal here the crucial role of Trim33 expression in the control of mature granulomonocytic differentiation. An important component of Trim33-deficient mice is the alteration of myeloid differentiation, as characterized by dysplastic features, abnormal granulocyte and monocyte maturation, and the expansion of CD11b(+)Ly6G(high)Ly6C(low) myeloid cells, which share some features with polymorphonuclear-myeloid-derived suppressor cells. Moreover, in Trim33(Δ/Δ) mice, we observed the alteration of CSF-1-mediated macrophage differentiation in association with the lack of Csf-1 receptor. Altogether, these results indicate that Trim33 deficiency leads to the expansion of a subset of myeloid cells characterizing the myelodysplastic/myeloproliferative neoplasm.
authors.affiliation: Inserm UMR 866, Labex LipSTIC Team, UFR des Sciences de Santé, Université Bourgogne Franche-Comté, Dijon, France; Department of Clinical Hematology, Hôpital Universitaire François-Mitterrand, Dijon, France.
authors.forename: Marie-Lorraine
authors.initials: ML
authors.lastname: Chrétien
authors.affiliation: Inserm UMR 866, Labex LipSTIC Team, UFR des Sciences de Santé, Université Bourgogne Franche-Comté, Dijon, France; Department of Clinical Hematology, Hôpital Universitaire François-Mitterrand, Dijon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Legouge
authors.affiliation: Inserm UMR 866, Labex LipSTIC Team, UFR des Sciences de Santé, Université Bourgogne Franche-Comté, Dijon, France.
authors.forename: Romain Z
authors.initials: RZ
authors.lastname: Martin
authors.affiliation: Cytometry Platform, Université Bourgogne Franche-Comté, Dijon, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Hammann
authors.affiliation: Inserm UMR 1098, UFR des Sciences de Santé, Labex LipSTIC Team, Université Bourgogne Franche-Comté, Dijon, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Trad
authors.affiliation: Inserm UMR 866, Labex LipSTIC Team, UFR des Sciences de Santé, Université Bourgogne Franche-Comté, Dijon, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Aucagne
authors.affiliation: Inserm UMR 866, Labex LipSTIC Team, UFR des Sciences de Santé, Université Bourgogne Franche-Comté, Dijon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Largeot
authors.affiliation: Inserm UMR 866, Labex LipSTIC Team, UFR des Sciences de Santé, Université Bourgogne Franche-Comté, Dijon, France; Department of Clinical Hematology, Hôpital Universitaire François-Mitterrand, Dijon, France.
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Bastie
authors.affiliation: Inserm UMR 866, Labex LipSTIC Team, UFR des Sciences de Santé, Université Bourgogne Franche-Comté, Dijon, France. Electronic address: Laurent.Delva@u-bourgogne.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Delva
authors.affiliation: Inserm UMR 866, Labex LipSTIC Team, UFR des Sciences de Santé, Université Bourgogne Franche-Comté, Dijon, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Quéré
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology* / Q000378:metabolism*; D016130:Immunophenotyping; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells; D038042:Myelopoiesis / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015415:Biomarkers; D014157:Transcription Factors; C491420:Trim33 protein, mouse