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| Status |
Public on Feb 24, 2019 |
| Title |
Cxcr3 expressing leukocytes are necessary for neurofibroma formation in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Plexiform neurofibroma is a major contributor to morbidity in Neurofibromatosis type I (NF1) patients. Macrophages and mast cells infiltrate neurofibroma, and data from mouse models implicate these leukocytes in neurofibroma development. Anti-inflammatory therapy targeting these cell populations has been suggested as a means to prevent neurofibroma development. Here, we compare gene expression in inflamed nerves from NF1 models which invariably form neurofibroma to those with inflammation driven by EGFR overexpression which rarely progresses to neurofibroma. We find that the chemokine Cxcl10 is uniquely up-regulated in NF1 mice that invariably develop neurofibroma. Global deletion of the CXCL10 receptor, Cxcr3, prevented neurofibroma development in these neurofibroma-prone mice. Cxcr3 expression localized to T cells and dendritic cells (DCs) in both inflamed nerves and neurofibromas. These data support a heretofore unappreciated role for T cells/DCs in neurofibroma initiation.
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| Overall design |
To identify cell populations associated with Cxcl10 expression, we utilized a single-cell RNA-Seq (scRNA-Seq) data set collected from 2-month Dhh-Cre;Nf1 fl/fl nerve/DRG using the 10x Genomics Chromium platform.
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| Contributor(s) |
Fletcher JS, Wu J, Jessen WJ, Pundavela J, Miller JA, Dombi E, Kim M, Rizvi TA, Chetal K, Salomonis N, Ratner N |
| Citation(s) |
30728335 |
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| Submission date |
Nov 20, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Nathan Salomonis |
| E-mail(s) |
nathan.salomonis@cchmc.org
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| Organization name |
Cincinnati Children's Hospital
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| Department |
Biomedical Informatics
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| Lab |
Nathan Salomonis
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| Street address |
3333 Burnet Avenue
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| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (1) |
| GSM3484259 |
2-month Dhh-Cre;Nf1 fl/fl nerve/DRG 10X Genomics single-cell RNA-Seq data set |
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| Relations |
| BioProject |
PRJNA507362 |
| SRA |
SRP171067 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE122730_RAW.tar |
96.3 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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