|
| Status |
Public on Oct 04, 2010 |
| Title |
TGF-β1 Accelerates Dendritic Cell Differentiation from Common Dendritic Cell Progenitors (CDPs) and Directs Subset Specification Towards Conventional Dendritic Cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
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-β1 (TGF-β1) impacts on CDPs and directs their differentiation towards cDCs. Genome-wide gene expression profiling of TGF-β1-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-β1 also induced the transcription factor inhibitor of differentiation/DNA binding 2 (Id2) that suppresses pDC development. Thus, TGF-β1 directs CDP differentiation into cDC by inducing both cDC instructive factors and pDC inhibitory factors.
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| |
|
| Overall design |
20 samples in total.
Multipotent progenitor
- MPP_1
- MPP_2
Common dendritic cell progenitor
- CDP_1
- CDP_2
Plasmacytoid dendritic cell
- pDC_1
- pDC_2
Conventional dendritic cell
- cDC_1
- cDC_2
In vivo common dendritic cell progenitor
- In vivo CDP_1
- In vivo CDP_2
Untreated common dendritic cell progenitor (CDP)
- CDP_0h_1
- CDP_0h_2
TGF-beta1 treated (4 hours) CDP
- CDP_4h_1
- CDP_4h_2
TGF-beta1 treated (8 hours) CDP
- CDP_8h_1
- CDP_8h_2
TGF-beta1 treated (12 hours) CDP
- CDP_12h_1
- CDP_12h_2
TGF-beta1 treated (24 hours) CDP
- CDP_24h_1
- CDP_24h_2
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| |
|
| Contributor(s) |
Felker P, Sere K, Lin Q, Becker C, Hristov M, Hieronymus T, Zenke M |
| Citation(s) |
20881193 |
| Submission date |
Jun 18, 2010 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Martin Zenke |
| E-mail(s) |
Martin.Zenke@rwth-aachen.de
|
| Phone |
+49-241-80 80760
|
| Organization name |
Institute for Biomedical Engineering
|
| Department |
Cell Biology
|
| Street address |
Universitatsklinikum Aachen, RWTH
|
| City |
Aachen |
| State/province |
NRW |
| ZIP/Postal code |
52074 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
|
| Samples (20)
|
| GSM461424 |
Multipotent progenitor sample 1 (MPP_1) |
| GSM461426 |
Multipotent progenitor sample 2 (MPP_2) |
| GSM461428 |
Common dendritic cell progenitor sample 1 (CDP_1) |
| GSM461430 |
Common dendritic cell progenitor sample 2 (CDP_2) |
| GSM461431 |
Conventional dendritic cell sample 1 (cDC_1) |
| GSM461451 |
Conventional dendritic cell sample 2 (cDC_2) |
| GSM461452 |
Plasmacytoid dendritic cell sample 1 (pDC_1) |
| GSM461453 |
Plasmacytoid dendritic cell sample 2 (pDC_2) |
| GSM557486 |
untreated common dendritic cell progenitor sample 1 (CDP_0h_1) |
| GSM557487 |
untreated common dendritic cell progenitor sample 2 (CDP_0h_2) |
| GSM557488 |
TGF-beta1 treated (4 hours) common dendritic cell progenitor sample 1 (CDP_4h_1) |
| GSM557489 |
TGF-beta1 treated (4 hours) common dendritic cell progenitor sample 2 (CDP_4h_2) |
| GSM557490 |
TGF-beta1 treated (8 hours) common dendritic cell progenitor sample 1 (CDP_8h_1) |
| GSM557491 |
TGF-beta1 treated (8 hours) common dendritic cell progenitor sample 2 (CDP_8h_2) |
| GSM557492 |
TGF-beta1 treated (12 hours) common dendritic cell progenitor sample 1 (CDP_12h_1) |
| GSM557493 |
TGF-beta1 treated (12 hours) common dendritic cell progenitor sample 2 (CDP_12h_2) |
| GSM557494 |
TGF-beta1 treated (24 hours) common dendritic cell progenitor sample 1 (CDP_24h_1) |
| GSM557495 |
TGF-beta1 treated (24 hours) common dendritic cell progenitor sample 2 (CDP_24h_2) |
| GSM557496 |
In vivo common dendritic cell progenitor (In vivo CDP_1) sample 1 |
| GSM557497 |
In vivo common dendritic cell progenitor (In vivo CDP_2) sample 2 |
|
| Relations |
| BioProject |
PRJNA128559 |
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