1. Academic Validation
  2. The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development

The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development

  • J Exp Med. 2004 Dec 6;200(11):1503-9. doi: 10.1084/jem.20041231.
Remko Schotte 1 Maho Nagasawa Kees Weijer Hergen Spits Bianca Blom
Affiliations

Affiliation

  • 1 Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, Netherlands.
Abstract

A number of transcription factors that act as molecular switches for hematopoietic lineage decisions have been identified. We recently described the ETS transcription factor Spi-B to be exclusively expressed in plasmacytoid dendritic cells (pDCs), but not in myeloid DCs. To assess whether Spi-B is required for pDC development we used an RNA interference knock down approach to specifically silence Spi-B protein synthesis in CD34(+) precursor cells. We observed that a knock down of Spi-B mRNA strongly inhibited the ability of CD34(+) precursor cells to develop into pDCs in both in vitro assays as well as in vivo upon injection into recombination activating gene 2(-/-) gamma common(-/-) mice. The observed effects were restricted to the pDC lineage as the differentiation of pro-B cells and CD14(+) myeloid cells was not inhibited but slightly elevated by Spi-B knock down. Knock down of the related ETS factor PU.1 also inhibited in vitro development of CD34(+) cells into pDCs. However, in contrast to Spi-B, PU.1 knock down inhibited B cell and myeloid cell development as well. These results identify Spi-B as a key regulator of human pDC development.

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