Oligodendrocyte progenitor cells become regionally diverse and heterogeneous with age
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ABSTRACT:
PROVIDER: PRJNA495612 | ENA |
REPOSITORIES: ENA
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Project description:Oligodendrocyte progenitor cells (OPCs), which differentiate into myelinating oligodendrocytes during central nervous system (CNS) development, are the main proliferative cells in the adult brain. OPCs are conventionally considered a homogeneous population, particularly with respect to their electrophysiological properties, but this has been debated. We show, by using single-cell electrophysiological recordings, that OPCs start out as a homogeneous population, but become functionally heterogeneous, varying both within and between brain regions and with age. These electrophysiological changes in OPCs correlate with the differentiation potential of OPCs; thus, they may underlie the differentiational differences in OPCs between regions and likewise differentiation failure with age.
2019-01-15 | GSE121083 | GEO
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Project description:Bulk RNA-seq of highly pure regionally specified human pluripotent stem cell-derived astrocytes
2019-06-29 | GSE133489 | GEO
Project description:Stem cell biology has garnered much attention due to its potential to impact human health through disease modeling and cell replacement therapy. This is especially pertinent to myelin-related disorders such as multiple sclerosis and leukodystrophies where restoration of normal oligodendrocyte function could provide an effective treatment. Progress in myelin repair has been constrained by the difficulty in generating pure populations of oligodendrocyte progenitor cells (OPCs) in sufficient quantities. Pluripotent stem cells theoretically provide an unlimited source of OPCs but significant advances are currently hindered by heterogeneous differentiation strategies that lack reproducibility. Here we provide a platform for the directed differentiation of pluripotent mouse epiblast stem cells (EpiSCs) through a defined series of developmental transitions into a pure population of highly expandable OPCs in ten days. These OPCs robustly differentiate into myelinating oligodendrocytes both in vitro and in vivo. Our results demonstrate that pluripotent stem cells can provide a pure population of clinically-relevant, myelinogenic oligodendrocytes and offer a tractable platform for defining the molecular regulation of oligodendrocyte development, drug screening, and potential cell-based remyelinating therapies. 6 total samples were analyzed. Pluripotent epiblast stem cells (EpiSCs) were differentiated to patterned neural rosettes, oligodendrocyte progenitor cells (OPCs), and oligodendrocytes. OPCs and oligodedrocytes were analyzed at two separate passages (3 and 11).
2011-10-02 | E-GEOD-31562 | biostudies-arrayexpress
Project description:SOX transcription factors have important roles during astrocyte and oligodendrocyte development, but how glial genes are specified and activated in a sub-lineage specific fashion remains unknown. To address this question, we have defined glial specific gene expression in the developing spinal cord using single-cell RNA-sequencing. Moreover, conducting ChIP-seq analyses we show that these glial gene sets are extensively preselected already in multipotent neural precursor cells through the prebinding by SOX3. In the subsequent lineage-restricted glial precursor cells, astrocyte genes become additionally targeted by SOX9 at DNA-regions strongly enriched for Nfi binding-motifs, whereas oligodendrocyte genes become prebound by SOX9 only, at sites that during oligodendrocyte maturation are targeted by SOX10. Interestingly, reporter gene assays and functional studies in the spinal cord revealed that SOX3 binding represses the synergistic activation of astrocyte genes by SOX9 and NFIA, whereas oligodendrocyte genes are activated in a combinatorial manner by SOX9 and SOX10. These genome-wide studies demonstrate how sequentially expressed SOX proteins act on lineage-specific regulatory DNA-elements to coordinate glial gene expression both in a temporal and sub-lineage specific fashion.
2018-08-02 | GSE117997 | GEO
Project description:The influence of Positron-Emission-Tomography (PET) on the surgical treatment of loco-regionally recurrent colorectal cancer (LRRCRC) remains obscure and deserves further investigation.
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Project description:The mechanisms underlying the specification of oligodendrocyte fate from multipotent neural progenitor cells (NPCs) in developing human brain are unknown. In this study, we sought to identify antigens sufficient to distinguish NPCs free from oligodendrocyte progenitor cells (OPCs). We investigated the potential overlap of NPC and OPC antigens using multicolor fluorescence-activated cell sorting (FACS) for CD133/PROM1, A2B5, and CD140a/PDGFaR antigens. Surprisingly, we found that CD133, but not A2B5, was capable of enriching for OLIG2 expression, Sox10 enhancer activity, and oligodendrocyte potential. As a subpopulation of CD133- positive cells expressed CD140a, we asked whether CD133 enriched bone fide NPCs regardless of CD140a expression. We found that CD133+CD140a- cells were highly enriched for neurosphere initiating cells and were multipotent. Importantly, when analyzed immediately following isolation, CD133+CD140a- NPCs lacked the capacity to generate oligodendrocytes. In contrast, CD133+CD140a+ cells were OLIG2-expressing OPCs capable of oligodendrocyte differentiation, but formed neurospheres with lower efficiency and were largely restricted to glial fate. Gene expression analysis further confirmed the stem cell nature of CD133+CD140a- cells. As human CD133+ cells comprised both NPCs and OPCs, CD133 expression alone cannot be considered a specific marker of the stem cell phenotype, but rather comprises a heterogeneous mix of glial restricted as well as multipotent neural precursors. In contrast, CD133/CD140a-based FACS permits the separation of defined progenitor populations and the study of neural stem and oligodendrocyte fate specification in the human brain. 12 samples, 4 groups (FACS-sorted cell populations),3 replicates in each group, each replicate is from a separate patient sample
2013-04-23 | E-GEOD-40676 | biostudies-arrayexpress
Project description:Regionally specified human pluripotent stem cell-derived astrocytes
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Project description:We used RNA sequencing to examine the transcriptional changes in differentiated oligodendrocytes, oligodendrocyte precursor cells, astroctytes, and microglia after blocking exocytosis from oligodendrocyte-lineage cells
2022-10-31 | GSE168569 | GEO
Project description:The leptomeninges envelop the central nervous system and contribute to brain homeostasis by producing trophic factors and regulating entrance of cells, factors and agents, immune responses and cerebrospinal fluid production. We report that leptomeninges from adult mice are regionally patterned. Leptomeninges dissected from anterior or posterior aspects of the forebrain grown in hetero- or homo-typic culture with anterior and posterior cortical cells demonstrate differences in ability to support survival of neuronal subsets and proliferation of progenitors for astrocytes and oligodendrocytes. Meningeal support changes with age: co-culture with 18-month old leptomeninges reduced numbers of cortical progenitor cells and neurons but increased astrocyte expansion. Analysis of cytokine secretion and single cell RNA-sequencing revealed differences in anterior versus posterior, young versus old meningeal factors and composition. These data demonstrate that adult leptomeninges are regionally patterned in cell composition and functional properties, and suggest that meningeal deficits may contribute to brain aging and disease.
2021-11-01 | GSE139922 | GEO