Human Gene Set: GSE22432_MULTIPOTENT_VS_COMMON_DC_PROGENITOR_DN


Standard name GSE22432_MULTIPOTENT_VS_COMMON_DC_PROGENITOR_DN
Systematic name M7822
Brief description Genes down-regulated in amplified: multipotent progenitors versus common dendritic cell progenitors.
Full description or abstract Dendritic cells (DCs) in lymphoid tissue comprise conventional DCs (cDCs) and plasmacytoid DCs (pDCs) that develop from common DC progenitors (CDPs). CDPs are Flt3+c-kitintM-CSFR+ and reside in bone marrow. Here we describe a two-step culture system that recapitulates DC development from c-kithiFlt3-/lo multipotent progenitors (MPPs) into CDPs and further into cDC and pDC subsets. MPPs and CDPs are amplified in vitro with Flt3 ligand, stem cell factor, hyper-IL-6 and insulin- like growth factor-1. The four-factor cocktail readily induces self-renewal of MPPs and their progression into CDPs and has no self-renewal activity on CDPs. The amplified CDPs respond to all known DC poietins and generate all lymphoid tissue DCs in vivo and in vitro. Additionally, in vitro CDPs recapitulate the cell surface marker and gene expression profile of in vivo CDPs and possess a DC-primed transcription profile. Transforming growth factor-?1 (TGF-?1) impacts on CDPs and directs their differentiation towards cDCs. Genome-wide gene expression profiling of TGF-?1-induced genes identified transcription factors, such as interferon regulatory factor-4 (IRF-4) and RelB, that are implicated as instructive factors for cDC subset specification. TGF-?1 also induced the transcription factor inhibitor of differentiation/DNA binding 2 (Id2) that suppresses pDC development. Thus, TGF-?1 directs CDP differentiation into cDC by inducing both cDC instructive factors and pDC inhibitory factors.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 20881193   Authors: Felker P,Seré K,Lin Q,Becker C,Hristov M,Hieronymus T,Zenke M
Exact source GSE22432_3611_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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identifier namespace		 HUMAN_GENE_SYMBOL
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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