Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate

Xiaodi Wu, Carlos G. Briseño, Gary E. Grajales-Reyes, Malay Haldar, Arifumi Iwata, Nicole M. Kretzer, K. C. Wumesh, Roxane Tussiwand, Yujiro Higashi, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Dendritic cells (DCs) and monocytes develop from a series of bone-marrow-resident progenitors in which lineage potential is regulated by distinct transcription factors. Zeb2 is an E-box-binding protein associated with epithelial-mesenchymal transition and is widely expressed among hematopoietic lineages. Previously, we observed that Zeb2 expression is differentially regulated in progenitors committed to classical DC (cDC) subsets in vivo. Using systems for inducible gene deletion, we uncover a requirement for Zeb2 in the development of Ly-6Chi monocytes but not neutrophils, and we show a corresponding requirement for Zeb2 in expression of the M-CSF receptor in the bone marrow. In addition, we confirm a requirement for Zeb2 in development of plasmacytoid DCs but find that Zeb2 is not required for cDC2 development. Instead, Zeb2 may act to repress cDC1 progenitor specification in the context of inflammatory signals.

Original languageEnglish
Pages (from-to)14775-14780
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number51
DOIs
StatePublished - Dec 20 2016

Keywords

  • Monocyte
  • Plasmacytoid dendritic cell
  • Transcription factor

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