Ikaros cooperates with Notch activation and antagonizes TGFß signaling to promote pDC development.
PLoS Genet
; 14(7): e1007485, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-30001316
ABSTRACT
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 TGFß function to promote pDC differentiation from CDPs. Strikingly, Ikaros-deficient CDPs and pDCs express a cDC-like transcriptional signature that is correlated with TGFß activation, suggesting that Ikaros is an upstream negative regulator of the TGFß 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 TGFß-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Diferenciação Celular
/
Fator de Crescimento Transformador beta
/
Fator de Transcrição Ikaros
/
Receptores Notch
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article