Spontaneous direct fate conversion of neuroblasts into oligodendrocytes upon demyelination in the adult mouse brain
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PROVIDER: PRJNA539868 | ENA |
REPOSITORIES: ENA
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Project description:After demyelinating insult, the neuronal progenitors of the adult mouse sub-ventricular zone (SVZ) called neuroblasts convert into oligodendrocytes that participate to the remyelination process. We use this rare example of spontaneous fate conversion to identify the molecular mechanisms governing these processes. Using single cell RNA-sequencing, we show that SVZ neuroblasts fate conversion proceeds directly, through formation of a non-proliferating transient cellular state co-expressing markers of both neuronal and oligodendrocyte identities. Transition between the two identities starts immediately after demyelination and occurs gradually, by a stepwise upregulation/downregulation of key TFs and chromatin modifiers. Each step of this fate conversion involves fine adjustments of the transcription and translation machineries as well as tight regulation of metabolism and migratory behaviors. Together, these data constitute the first in-depth analysis of a spontaneous direct cell fate conversion in the adult mammalian CNS.
2019-11-25 | GSE130355 | GEO
Project description:We report the generation of myelinating human oligodendrocytes from dermal fibroblasts using a direct lineage conversion technique.
2022-05-20 | GSE203451 | GEO
Project description:Oligodendrocytes are cells from the central nervous system that can be grouped into precursors, myelin-forming, and non-myelinating perineuronal. The function of perineuronal oligodendrocytes is unknown; it was suggested that they can ensheath denuded axons. We tested this hypothesis. Using cell-specific tags, microarray technology and bioinformatics tools to identify gene expression differences between these subpopulations allowed us to capture the genetic signature of perineuronal oligodendrocytes. Here we report that perineuronal oligodendrocytes are configured for a dual role. As perineuronal, they integrate a repertoire of transcripts designed to create a cell with its own physiological agenda. But they maintain a reservoir of untranslated transcripts encoding the major myelin proteins for â we speculate â a pathological eventuality. We posit that the signature molecules PDGFR-αβ, cytokine PDGF-CC, and the transcription factor Pea3 used â among others - to define the non-myelinating phenotype, may be critical for mounting a myelinating programme during demyelination. Harnessing this capability is of therapeutic value for diseases such as multiple sclerosis. This is the first molecular characterization of perineuronal oligodendrocytes. Experiment Overall Design: Flow Cytometry was used to isolate A2B5/OTMP+ oligodendrocytes from postnatal day 7 rat brain. 4 bioloical replicates were obtained. This data can be compared to the previously submitted oligodendrocyte expression data (GSE5940).
2008-06-18 | E-GEOD-11277 | biostudies-arrayexpress
Project description:Direct conversion of pericytes (PCs) into induced oligodendrocytes (iOPCs) by ectopic expression of Olig2 and Sox10 (2F) was assessed by chromatin accessibility profiling (by ATAC-seq). Samples were collected before and after direct conversion (at 3 different time points/passages - p5, p15 and p25).
2021-03-07 | E-MTAB-8452 | biostudies-arrayexpress
Project description:Direct conversion of pericytes (PCs) or mouse embryonic fibroblasts (MEFs) into induced oligodendrocytes (iOPCs) by ectopic expression of Olig2, Sox10 and Nkx6.2 was assessed by transcriptome profiling (RNA-seq). Samples were collected before and after direct conversion (for PCs at 3 different time points/passages - p5, p15 and p25)
2021-03-07 | E-MTAB-8453 | biostudies-arrayexpress
Project description: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, M-bM-^@M-^\quiescentM-bM-^@M-^] 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 M-bM-^@M-^\activatedM-bM-^@M-^] adult OPCs, genes of the innate immune response, IL1M-NM-2 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 IL1M-NM-2 and CCL2 M-bM-^@M-^\accountM-bM-^@M-^] 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 M-bM-^@M-^\quiescentM-bM-^@M-^] adult OPCs, which become as mobile as M-bM-^@M-^\activatedM-bM-^@M-^] 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 M-bM-^@M-^\activatedM-bM-^@M-^] 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. 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.
2014-11-06 | E-GEOD-48872 | biostudies-arrayexpress
Project description:Generation of functional human oligodendrocytes from dermal fibroblasts by direct lineage conversion
| PRJNA840883 | ENA
Project description:Oligodendrocytes are cells from the central nervous system that can be grouped into precursors, myelin-forming, and non-myelinating perineuronal. The function of perineuronal oligodendrocytes is unknown; it was suggested that they can ensheath denuded axons. We tested this hypothesis. Using cell-specific tags, microarray technology and bioinformatics tools to identify gene expression differences between these subpopulations allowed us to capture the genetic signature of perineuronal oligodendrocytes. Here we report that perineuronal oligodendrocytes are configured for a dual role. As perineuronal, they integrate a repertoire of transcripts designed to create a cell with its own physiological agenda. But they maintain a reservoir of untranslated transcripts encoding the major myelin proteins for – we speculate – a pathological eventuality. We posit that the signature molecules PDGFR-αβ, cytokine PDGF-CC, and the transcription factor Pea3 used – among others - to define the non-myelinating phenotype, may be critical for mounting a myelinating programme during demyelination. Harnessing this capability is of therapeutic value for diseases such as multiple sclerosis. This is the first molecular characterization of perineuronal oligodendrocytes. Keywords: developmental
2008-06-01 | GSE11277 | GEO
Project description:How microglia respond and regulate demyelination is not fully understood. To understand how microglia respond during demyelination, we fed mice cuprizone and assessed the response of genetically fate-mapped microglia. Cuprizone-induced demyelination generated a robust microglial response. We conducted single-cell RNA sequencing and identified several cuprizone-associated microglia (CAM) clusters during demyelination. These clusters expressed a transcriptomic signature indicative of cytokine regulation and reactive oxygen species production with altered lysosomal and metabolic changes consistent with ongoing phagocytosis. To understand how microglia contribute to the clearance of dead oligodendrocytes, we ablated microglia starting at the peak of cell death. We used the viability dye acridine orange and monitored apoptotic and lytic cell morphologies after microglial ablation and found that microglia preferentially phagocytose lytic carcasses. In culture, microglia exposed to lytic carcasses partially recapitulated the CAM state, suggesting that phagocytosis contributes to this distinct microglial state during cuprizone demyelination.
2022-08-08 | GSE207570 | GEO
Project description:A brain consists of numerous distinct neurons arising from a limited number of progenitors, called neuroblasts in Drosophila. Each neuroblast makes a specific neuronal lineage. To unravel the transcriptional networks that underlie the development of distinct neuroblast lineages, we marked and isolated lineage-specific neuroblasts for RNA sequencing. We labeled particular neuroblasts throughout neurogenesis by activating a conditional neuroblast driver in specific lineages using various intersection strategies. The targeted neuroblasts were efficiently recovered using a custom-built device for robotic single cell picking. Transcriptome analysis on the mushroom body, antennal lobe, and type II neuroblasts besides non-selective neuroblasts, neurons, and glia revealed a rich repertoire of transcription factors expressed among neuroblasts in diverse patterns. In addition to those likely pan-neuroblast transcription factors, there exist many transcription factors selectively enriched or repressed in certain neuroblasts. The unique combinations of transcription factors present in different neuroblasts may govern the diverse lineage-specific neuron fates
2015-12-29 | GSE71104 | GEO