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PMID: 16973960 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Regulation of dendritic-cell differentiation by bone marrow stroma via different Notch ligands.

Blood ·Vol. 109 ·No. 2 ·2007-01-15 ·Pages 507-15

Cheng P, Nefedova Y, Corzo CA, Gabrilovich DI

Abstract

Notch is a major factor mediating interaction between hematopoietic progenitor cells (HPCs) and bone marrow stroma (BMS). However its contribution to dendritic cell (DC) differentiation is controversial. We found that main Notch ligands Delta-1 and Jagged-1 had the opposite effect on DC differentiation. Delta-1 promoted generation of fully differentiated DCs, whereas Jagged-1 stimulated accumulation of DC precursors but prevented their transition to terminally differentiated DCs. BMS expressed a substantially higher level of Jagged-1 than Delta-1. Just the opposite expression pattern was observed in spleen stroma (SS). The BMS effect on DC differentiation was similar to that of Jagged-1, whereas the effect of SS was similar to the effect of Delta-1. Down-regulation of Jagged-1 in BMS substantially increased DC differentiation. Experiments in vivo with adoptive transfer of DC precursors further supported the different roles of BMS and SS in DC development. Jagged-1 and Delta-1 equally activated CBF-1/RBPJkappa transcription factor, which is a major Notch target. However, they produced a different pattern of activation of Notch target gene Hes1. Overexpression of Hes1 resulted in increased DC differentiation from HPCs. Thus, this study not only revealed the different role of Notch ligands in DC differentiation but also may provide a new insight into regulation of DC differentiation by BMS.

MeSH Terms
Animals Bone Marrow Cells/cytology Calcium-Binding Proteins/genetics,metabolism Cell Differentiation/immunology Cell Line Dendritic Cells/cytology,immunology Down-Regulation Female Gene Expression Regulation/genetics Intercellular Signaling Peptides and Proteins/genetics,metabolism Intracellular Signaling Peptides and Proteins Jagged-1 Protein Ligands Membrane Proteins/genetics,metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL NIH 3T3 Cells Serrate-Jagged Proteins Spleen/cytology Stromal Cells/cytology
Chemicals
Calcium-Binding Proteins Intercellular Signaling Peptides and Proteins Intracellular Signaling Peptides and Proteins Jag1 protein, mouse Jagged-1 Protein Ligands Membrane Proteins Serrate-Jagged Proteins delta protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cheng Pingyan
H. Lee Moffitt Cancer Center, Department of Interdisciplinary Oncology, University of South Florida, MRC 2067, 12902 Magnolia Dr, Tampa, FL 33612, USA.
Nefedova Yulia
Corzo Cesar A
Gabrilovich Dmitry I
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2006-05-025601
Published
2007-01-15
Epub
2006-00-14
Pages
507-15
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1766374
Subset
IM
Grants
NCI NIH HHS · R01 CA100062 · United States
NCI NIH HHS · 1R01CA100062 · United States
External Links
PubMed source DOI: 10.1182/blood-2006-05-025601 PMC Full Text View journal details
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