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Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-04-1034. This Article Full Text (PDF) All Versions of this Article: 2003-04-1034v1 102/12/3980    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cheng, P. Articles by Gabrilovich, D. Search for Related Content PubMed PubMed Citation Articles by Cheng, P. Articles by Gabrilovich, D. Social Bookmarking                   What's this? Submitted April 3, 2003 Accepted July 31, 2003 Notch signaling is necessary but not sufficient for differentiation of dendritic cells Pingyan Cheng, Yulia Nefedova, Lucio Miele, Barbara A Osborne, and Dmitry Gabrilovich* H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL, USA Department of Pharmocodynamics, University of Illinois, Chicago, IL, USA Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, USA * Corresponding author; email: dgabril{at}moffitt.usf.edu. The Notch family of receptors plays an important role in regulation of cell differentiation via direct contact between hematopoietic progenitor cells (HPC) and bone marrow stroma (BMS). However the precise contribution of Notch in dendritic cell (DC) differentiation is controversial. In two different experimental systems using Notch-1 null embryionic stem cells and Notch-1 deficient HPCs we have found that Notch-1 is necessary for DC differentiation. However, activation of Notch-1 and Notch-2 with cell-bound Notch ligand did not result in differentiation of mature DCs or macrophages. Instead, it caused accumulation of immature myeloid cells. Removal of feeder cells resulted in rapid differentiation of DCs and macrophages. Addition of IL-4 into the culture dramatically increased accumulation of functionally potent DCs. LPS was not able to reproduce this effect. Thus, these data indicate that Notch signaling prevents differentiation of mature myeloid cells. Instead, it results in accumulation of precursors readily able to differentiate into mature DCs once the Notch signal is stopped (for instance after cell emigration from bone marrow) or/and in the presence of other additional differentiation signal provided by IL-4. Thus, this presents the first demonstration that Notch is required but not sufficient for DC differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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