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Status |
Public on Oct 12, 2016 |
Title |
Characterization of functional reprogramming during osteoclast development using quantitative proteomics and mRNA profiling |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
The innate immune system is the organism’s first line of defense against pathogens. Pattern recognition receptors (PRRs) are responsible for sensing the presence of pathogen-associated molecules. The prototypic PRRs, the membrane-bound receptors of the Toll-like receptor (TLR) family, recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response through signaling pathways that depend on the adaptor molecules MyD88 and TRIF. Deciphering the differences in the complex signaling events that lead to pathogen recognition and initiation of the correct response remains challenging. Here we report the discovery of temporal changes in the protein signaling components involved in innate immunity. Using an integrated strategy combining unbiased proteomics, transcriptomics and macrophage stimulations with three different PAMPs, we identified differences in signaling between individual TLRs and revealed specifics of pathway regulation at the protein level. In addition to forming macrophages and dendritic cells, monocytes in adult peripheral blood retain the ability to develop into osteoclasts, mature bone-resorbing cells. The extensive morphological and functional transformations that occur during osteoclast differentiation require substantial reprogramming of gene and protein expression. Here we employ -omic-scale technologies to examine in detail the molecular changes at discrete developmental stages in this process (precursor cells, intermediate osteoclasts, and multinuclear osteoclasts), quantitatively comparing their transcriptomes and proteomes.
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Overall design |
osteoclast precursor cells , intermediate osteoclasts, and multinuclear osteoclasts isolated after 5 days in culture, 4 replicates of each condition
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Contributor(s) |
An E, Narayanan M, Manes NP, Nita-Lazar A |
Citation(s) |
25044017 |
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Submission date |
Oct 11, 2016 |
Last update date |
Nov 24, 2017 |
Contact name |
Timothy G Myers |
E-mail(s) |
[email protected]
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Organization name |
National Institute of Allergy and Infectious Diseases
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Department |
Research Technologies Branch
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Lab |
Genomic Technologies Section
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Street address |
50 South Drive, Room 5509
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892-8005 |
Country |
USA |
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Platforms (1) |
GPL17543 |
Illumina MouseWG-6 v2.0 R2 expression beadchip |
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Samples (12)
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Relations |
BioProject |
PRJNA347645 |