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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jan 01, 2011 |
Title |
UV effects in mouse melanocytes |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Ultraviolet (UV) radiation is a major melanoma risk factor, yet underlying mechanisms remain poorly understood. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon-response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-gamma (IFN-gamma), but not type-I interferons. IFN-gamma was produced by macrophages recruited to neonatal skin by UVB-induced chemokine receptor Ccr2 ligands. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-gamma blockade abolished macrophage-associated melanoma growth and survival. IFN-gamma-producing macrophages were identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-gamma in promoting melanocytic cell survival/immunoevasion, and suggest IFN-gamma-R signaling represents a novel therapeutic melanoma target.
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Overall design |
Biologic replicates of UVA- and UVB-treated mouse melanocytes, as well as untreated mouse melanocytes and mouse keratinocytes, were used to define melanocyte expression signatures associated with UV treatment.
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Contributor(s) |
Davis SR, Zaidi MR, Meltzer PS, Merlino G |
Citation(s) |
21248750, 31949145 |
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Submission date |
Nov 05, 2010 |
Last update date |
Mar 14, 2020 |
Contact name |
Sean Davis |
E-mail(s) |
sdavis2@mail.nih.gov
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Phone |
301-435-2652
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Organization name |
National Cancer Institute
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Lab |
Genetics Branch
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Street address |
37 Convent Drive, Room 6138
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
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Platforms (1) |
GPL6103 |
Illumina mouseRef-8 v1.1 expression beadchip |
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Samples (30)
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GSM618249 |
Mouse melanocytes 01d after UVB treatment, rep1 |
GSM618250 |
Mouse melanocytes 01d after UVB treatment, rep2 |
GSM618251 |
Mouse melanocytes 06d after UVB treatment, rep1 |
GSM618252 |
Mouse melanocytes 06d after UVB treatment, rep2 |
GSM618253 |
Mouse melanocytes 01d after NoUV treatment, rep1 |
GSM618254 |
Mouse melanocytes 01d after NoUV treatment, rep2 |
GSM618255 |
Mouse melanocytes 06d after NoUV treatment, rep1 |
GSM618256 |
Mouse melanocytes 06d after NoUV treatment, rep2 |
GSM618257 |
Mouse melanocytes 06d after UVA treatment, rep1 |
GSM618258 |
Mouse melanocytes 06d after UVA treatment, rep2 |
GSM618259 |
Primary mouse keratinocytes, rep1 |
GSM618260 |
Primary mouse keratinocytes, rep2 |
GSM618261 |
Primary mouse keratinocytes, rep3 |
GSM618262 |
Mouse melanocytes 01d after UVA treatment, rep1 |
GSM618263 |
Mouse melanocytes 01d after UVA treatment, rep2 |
GSM618264 |
Mouse melanocytes 06d after UVA treatment, rep3 |
GSM618265 |
Mouse melanocytes 01d after NoUV treatment, rep3 |
GSM618266 |
Mouse melanocytes 06d after UVB treatment, rep3 |
GSM618267 |
Mouse melanocytes 01d after UVB treatment, rep3 |
GSM618268 |
Mouse melanocytes 01d after UVA treatment, rep3 |
GSM618269 |
Mouse melanocytes 06d after NoUV treatment, rep3 |
GSM618270 |
Mouse melanocytes 21d after UVB treatment, rep1 |
GSM618271 |
Mouse melanocytes 21d after UVB treatment, rep2 |
GSM618272 |
Mouse melanocytes 21d after UVB treatment, rep3 |
GSM618273 |
Mouse melanocytes 21d after NoUV treatment, rep1 |
GSM618274 |
Mouse melanocytes 21d after NoUV treatment, rep2 |
GSM618275 |
Mouse melanocytes 21d after NoUV treatment, rep3 |
GSM4411621 |
Mouse melanocytes flow sorted E17.5 pc, rep1 |
GSM4411622 |
Mouse melanocytes flow sorted E17.5 pc, rep2 |
GSM4411623 |
Mouse melanocytes flow sorted E17.5 pc, rep3 |
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Relations |
BioProject |
PRJNA134419 |
Supplementary file |
Size |
Download |
File type/resource |
GSE25164_GSM4411621-GSM4411623_non-normalized.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
GSE25164_RAW.tar |
3.4 Mb |
(http)(custom) |
TAR |
GSE25164_non-normalized.txt.gz |
7.0 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
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