Fiche publication
Date publication
juillet 2018
Journal
PLoS genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHAN Susan
,
Dr KASTNER Philippe
,
Dr KIRSTETTER Peggy
Tous les auteurs :
Mastio J, Simand C, Cova G, Kastner P, Chan S, Kirstetter P
Lien Pubmed
Résumé
Plasmacytoid and conventional dendritic cells (pDCs and cDCs) arise from monocyte and dendritic progenitors (MDPs) and common dendritic progenitors (CDPs) through gene expression changes that remain partially understood. Here we show that the Ikaros transcription factor is required for DC development at multiple stages. Ikaros cooperates with Notch pathway activation to maintain the homeostasis of MDPs and CDPs. Ikaros then antagonizes TGFβ function to promote pDC differentiation from CDPs. Strikingly, Ikaros-deficient CDPs and pDCs express a cDC-like transcriptional signature that is correlated with TGFβ activation, suggesting that Ikaros is an upstream negative regulator of the TGFβ pathway and a repressor of cDC-lineage genes in pDCs. Almost all of these phenotypes can be rescued by short-term in vitro treatment with γ-secretase inhibitors, which affects both TGFβ-dependent and -independent pathways, but is Notch-independent. We conclude that Ikaros is a crucial differentiation factor in early dendritic progenitors that is required for pDC identity.
Mots clés
Amyloid Precursor Protein Secretases, metabolism, Animals, Bone Marrow Transplantation, Cell Differentiation, genetics, Cell Line, Dendritic Cells, physiology, Down-Regulation, Hematopoietic Stem Cells, physiology, Ikaros Transcription Factor, genetics, Mice, Mice, Transgenic, Monocytes, physiology, Mutation, Receptors, Notch, metabolism, Signal Transduction, genetics, Transforming Growth Factor beta, metabolism, Up-Regulation
Référence
PLoS Genet.. 2018 Jul;14(7):e1007485
