The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development.
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.
Schotte
Remko
R
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, Netherlands.
Nagasawa
Maho
M
Weijer
Kees
K
Spits
Hergen
H
Blom
Bianca
B
D018952:Antigens, CD34 / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D022423:Myeloid Cells / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D013234:Stem Cells / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D000099232:Proto-Oncogene Protein Spi-1
D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C076877:SPIB protein, human