| First Author | Mastio J | Year | 2018 |
| Journal | PLoS Genet | Volume | 14 |
| Issue | 7 | Pages | e1007485 |
| PubMed ID | 30001316 | Mgi Jnum | J:263813 |
| Mgi Id | MGI:6189259 | Doi | 10.1371/journal.pgen.1007485 |
| Citation | Mastio J, et al. (2018) Ikaros cooperates with Notch activation and antagonizes TGFbeta signaling to promote pDC development. PLoS Genet 14(7):e1007485 |
| abstractText | 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 TGFbeta function to promote pDC differentiation from CDPs. Strikingly, Ikaros-deficient CDPs and pDCs express a cDC-like transcriptional signature that is correlated with TGFbeta activation, suggesting that Ikaros is an upstream negative regulator of the TGFbeta 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 gamma-secretase inhibitors, which affects both TGFbeta-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. |
