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| Status |
Public on May 03, 2017 |
| Title |
Immune-restricted epigenetic reader SP140 maintains macrophage identity and activation states critical to intestinal homeostasis [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Introduction: SP140 is a bromodomain/plant homeo domain (PHD)-containing reader with immune-restricted expression, and single nucleotide polymorphisms (SNPs) within SP140 associate with Crohn’s disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unknown.
Results: Individuals carrying CD-associated SNPs within SP140 had defective SP140 mRNA splicing, diminished SP140 protein, and severely suppressed innate immune signatures that stratified them from other CD patients.
Conclusion: SP140 is a critical orchestrator of macrophage identity, and a loss of SP140 due to genetic variation contributes to a molecularly defined subset of CD characterized by suppressed innate immunity.
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| Overall design |
RNA-seq of 8 samples of peripheral blood derived mononuclear cells from CD patients having T/T or C/C genotype for rs6716753 SNP, with and without LPS treatment. 4 samples from healthy individuals with and without LPS treatment. RNA-seq of human macrophages (total 8 samples from 2 independent donors) stimulated with IFNg for 24h, and LPS (100ng/mL) for 4 hours: siRNA mediated knockdown of SP140 versus controls.
RNA-seq of human macrophages (total 8 samples from 2 independent donors) stimulated with IFNg for 24h, and LPS (100ng/mL) for 4 hours for each condition: siRNA mediated knockdown of SP140 versus controls.
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| Contributor(s) |
Mehta S, Pantano L, Sui SH, Jeffrey KL |
| Citation |
Stuti Mehta, D. Alexander Cronkite, Megha Basavappa, Tahnee L. Saunders, Fatemeh Adiliaghdam, Hajera Amatullah, Sara A. Morrison, Jose D. Pagan, Robert M. Anthony, Pierre Tonnerre, Georg M. Lauer, James C. Lee, Sreehaas Digumarthi, Lorena Pantano, Shannan J. Ho Sui, Fei Ji, Ruslan Sadreyev, Chan Zhou, Alan C. Mullen, Vinod Kumar, Yang Li, Cisca Wijmenga, Ramnik J. Xavier, Terry K. Means, Kate L. Jeffrey (2017). Maintenance of macrophage transcriptional programs and intestinal homeostasis by epigenetic reader SP140. Science Immunology. March 3 Vol. 2, Issue 9, doi: 10.1126/sciimmunol.aag3160
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| Submission date |
Jun 15, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Lorena Pantano |
| E-mail(s) |
lpantano@iscb.org
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| Organization name |
Harvard Chan School of Public Health
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| Department |
Biostatistics
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| Lab |
Bioinformatic Core
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| Street address |
655 Huntington Ave
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE89876 |
Immune-restricted epigenetic reader SP140 maintains macrophage identity and activation states critical to intestinal homeostasis |
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| Relations |
| BioProject |
PRJNA325740 |
| SRA |
SRP076599 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE83381_RAW.tar |
10.2 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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