The Transcription Factor PU.1 Controls Dendritic Cell Development and Flt3 Cytokine Receptor Expression in a Dose-Dependent Manner
Details
Publication Year 2010-05-28, Volume 32, Issue #5, Page 628-641
Journal Title
IMMUNITY
Publication Type
Journal Article
Abstract
The transcription factor PU.1 plays multiple context and concentration dependent roles in lymphoid and myeloid cell development. Here we showed that PU.1 (encoded by Sfpi1) was essential for dendritic cell (DC) development in vivo and that conditional ablation of PU.1 in defined precursors, including the common DC progenitor, blocked Flt3 ligand-induced DC generation in vitro. PU.1 was also required for the parallel granulocyte-macrophage colony stimulating factor-induced DC pathway from early hematopoietic progenitors. Molecular studies demonstrated that PU.1 directly regulated Flt3 in a concentration-dependent manner, as Sfpi1(+/-) cells displayed reduced expression of Flt3 and impaired DC formation. These studies identify PU.1 as a critical regulator of both conventional and plasmacytoid DC development and provide one mechanism how altered PU.1 concentration can have profound functional consequences for hematopoietic cell development.
Publisher
CELL PRESS
Keywords
COLONY-STIMULATING FACTOR; MULTIPOTENT HEMATOPOIETIC PROGENITORS; BONE-MARROW CULTURES; LINEAGE-COMMITMENT; IN-VIVO; STEM-CELLS; TARGETED DISRUPTION; C/EBP-ALPHA; LIGAND; MACROPHAGE
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Refer to copyright notice on published article.


Creation Date: 2010-05-28 12:00:00
Last Modified: 0001-01-01 12:00:00
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