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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 06, 2014 |
| Title |
After demyelination in the adult CNS, oligodendrocyte precursor cells revert to an immature mRNA profile and express immune cues favoring their migration |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
In multiple sclerosis (MS) and experimental models of demyelination, myelin repair is mostly achieved by oligodendrocyte precursor cells (OPCs). To gain insight into the biological specificity of these adult precursors, in the perspective to better understand why remyelination often fails in MS, we performed a micro-array analysis on purified populations of murine OPCs and oligodendrocytes. We demonstrated that, in a control environment, “quiescent” adult OPCs are more mature than neonatal OPCs, with a mRNA profile closer to oligodendrocytes. However, when demyelination occurs, adult OPCs revert to an immature gene expression profile, acquiring higher migration and faster differentiation capacities. Among the many genes differentially regulated by these “activated” adult OPCs, genes of the innate immune response, IL1β and CCL2 were strongly upregulated after demyelination, with increased protein expression in experimental demyelinating lesions and within MS plaques. We first showed in vitro that both IL1β and CCL2 “account” for increased migration capacities of adult OPCs, an effect that is suppressed by corresponding receptor blockade. Focusing on Ccl2, we then demonstrated that lentiviral over-expression of Ccl2 increases motility of “quiescent” adult OPCs, which become as mobile as “activated” adult OPCs. This in vitro gain of function was further confirmed in vivo, by showing an increased migration of grafted CG4 oligodendroglial cells over-expressing-Ccl2. These results, demonstrating that “activated” adult OPCs upregulate immune cues favouring their migration, open new perspective of demyelination-induced immune-glial interactions, which might influence both oligodendroglial and inflammatory cells, therefore play a key role in lesion fate in multiple sclerosis.
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| Overall design |
In this study, we loaded purified population of progenitors of oligodendrocytes (OPCs) (from neonatal, 2-month-old, 2-month-old and cuprizone-treated brains) and of mature oligodendrocytes (OLs) (2-month-old brains) and compared their gene expression. We compared gene expression of neonatal OPCs, adult OPCs, adult OLs and adult OPCs from control conditions and from demyelinating conditions, using 3 to 4 independant replicates in each group.
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| Contributor(s) |
Moyon S, Aigrot MS, Trotter M, Huang J, Dauphinot L, Debussy AL, Parsadaniantz SM, Franklin R, Lubetzki C |
| Citation(s) |
25568099, 34099715, 35822550 |
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| Submission date |
Jul 15, 2013 |
| Last update date |
Aug 24, 2022 |
| Contact name |
Sarah Moyon |
| E-mail(s) |
smoyon@gc.cuny.edu
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| Organization name |
CUNY ASRC
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| Department |
Neuroscience
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| Lab |
Casaccia
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| Street address |
85 St Nicholas Terrace
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10031 |
| Country |
USA |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (18)
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| GSM1186193 |
adult progenitor of oligodendrocytes_rep1 |
| GSM1186194 |
adult progenitor of oligodendrocytes_rep2 |
| GSM1186195 |
adult progenitor of oligodendrocytes_rep3 |
| GSM1186196 |
adult progenitor of oligodendrocytes_rep4 |
| GSM1186197 |
neonatal progenitor of oligodendrocytes_rep1 |
| GSM1186198 |
neonatal progenitor of oligodendrocytes_rep2 |
| GSM1186199 |
neonatal progenitor of oligodendrocytes_rep3 |
| GSM1186200 |
adult oligodendrocytes_rep1 |
| GSM1186201 |
adult oligodendrocytes_rep2 |
| GSM1186202 |
adult oligodendrocytes_rep3 |
| GSM1186203 |
adult oligodendrocytes_rep4 |
| GSM1186204 |
adult progenitor of oligodendrocytes from cuprizone-treated brains_rep1 |
| GSM1186205 |
adult progenitor of oligodendrocytes from cuprizone-treated brains_rep2 |
| GSM1186206 |
adult progenitor of oligodendrocytes from cuprizone-treated brains_rep3 |
| GSM1186207 |
adult progenitor of oligodendrocytes from cuprizone-treated brains_rep4 |
| GSM1186208 |
adult progenitor of oligodendrocytes from control brains_rep1 |
| GSM1186209 |
adult progenitor of oligodendrocytes from control brains_rep2 |
| GSM1186210 |
adult progenitor of oligodendrocytes from control brains_rep3 |
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| Relations |
| BioProject |
PRJNA212046 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE48872_RAW.tar |
119.3 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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