CD140a+ human glial progenitor cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Fraser Sim
PROVIDER: E-GEOD-29368 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Glial progenitor cells (GPCs) pervade the human brain. These cells express gangliosides recognized by MAb A2B5, and some but not all can generate oligodendrocytes. Since some A2B5+ GPCs express PDGFa receptor (PDGFRa), which is critical to oligodendrocyte development, we asked if PDGFRa-directed sorting might isolate oligodendrocyte-competent progenitors. We used FACS to sort PDGFRa+ cells from the second trimester fetal human forebrain, based on expression of the PDGFRa epitope CD140a. CD140a+ cells could be maintained as mitotic progenitors that could be instructed to either oligodendrocyte or astrocyte phenotype. Transplanted CD140a+ cells robustly myelinated the hypomyelinated shiverer mouse brain. Microarray confirmed that CD140a+ cells differentially expressed PDGFRA, NG2, OLIG1/2, NKX2.2 and SOX2. Some expressed CD9, thereby defining a CD140a+/CD9+ fraction of oligodendrocyte-biased progenitors. CD140a+ cells differentially expressed genes of the PTN-PTPRZ1, wnt, notch and BMP pathways, suggesting the interaction of self-renewal and fate-restricting pathways in these cells, while identifying targets for their mobilization and instruction.
2011-10-01 | GSE29368 | GEO
Project description:Glial progenitor cells (GPCs) of the adult human white matter, which express gangliosides recognized by monoclonal antibody A2B5, are a potential source of glial tumors of the brain. We used A2B5-based sorting to extract progenitor-like cells from a range of human glial tumors, that included low-grade glioma, oligodendroglioma, oligo-astrocytomas, anaplastic astrocytoma, and glioblastoma multiforme. The A2B5+ tumor cells proved tumorigenic upon orthotopic xenograft, and the tumors generated reflected the phenotypes of those from which they derived. Expression profiling revealed that A2B5+ tumor progenitors expressed a cohort of genes by which they could be distinguished from A2B5+ GPCs isolated from normal adult white matter. Most of the genes differentially expressed by glioma-derived A2B5+ cells varied as a function of tumor stage; however, a small number were invariably expressed at all stages of gliomagenesis. These glioma progenitor-associated genes included CD24, SIX1 and EYA1, which were up-regulated at all stages of gliomagenesis, and MTUS1 and SPOCK3, which were down-regulated at all stages of tumor progression. qPCR and immunolabeling confirmed the differential expression of these genes in primary gliomas, while pathway analysis permitted their segregation into differentially active signaling pathways. By comparing the expression patterns of glial tumor progenitors to their identically-isolated normal homologues, we have identified a discrete set of oncogenic pathways by which glial tumorigenesis may be both better understood, and more efficiently targeted.
2013-05-16 | GSE29796 | GEO
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.
2013-04-23 | GSE40676 | GEO
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:Glial progenitor cells (GPCs) of the adult human white matter, which express gangliosides recognized by monoclonal antibody A2B5, are a potential source of glial tumors of the brain. We used A2B5-based sorting to extract progenitor-like cells from a range of human glial tumors, that included low-grade glioma, oligodendroglioma, oligo-astrocytomas, anaplastic astrocytoma, and glioblastoma multiforme. The A2B5+ tumor cells proved tumorigenic upon orthotopic xenograft, and the tumors generated reflected the phenotypes of those from which they derived. Expression profiling revealed that A2B5+ tumor progenitors expressed a cohort of genes by which they could be distinguished from A2B5+ GPCs isolated from normal adult white matter. Most of the genes differentially expressed by glioma-derived A2B5+ cells varied as a function of tumor stage; however, a small number were invariably expressed at all stages of gliomagenesis. These glioma progenitor-associated genes included CD24, SIX1 and EYA1, which were up-regulated at all stages of gliomagenesis, and MTUS1 and SPOCK3, which were down-regulated at all stages of tumor progression. qPCR and immunolabeling confirmed the differential expression of these genes in primary gliomas, while pathway analysis permitted their segregation into differentially active signaling pathways. By comparing the expression patterns of glial tumor progenitors to their identically-isolated normal homologues, we have identified a discrete set of oncogenic pathways by which glial tumorigenesis may be both better understood, and more efficiently targeted. Samples originating from patients with matched disease and/or pathology were considered as replicates either on the basis of exact tumor phenotype, tumor grade, or tumor vs. normal tissue samples.
2013-05-16 | E-GEOD-29796 | biostudies-arrayexpress
Project description:Oligodendrocytes undergo extensive changes as they differentiate from progenitors into myelinating cells. To better understand the; molecular mechanisms underlying this transformation, we performed a comparative analysis using gene expression profiling of A2B5+; oligodendrocyte progenitors and O4+ oligodendrocytes. Cells were sort-purified ex vivo from postnatal rat brain using flow cytometry. Using Affymetrix microarrays, 1707 transcripts were identified with a more than twofold increase in expression inO4+oligodendrocytes. Many genes required for oligodendrocyte differentiation were upregulated in O4+ oligodendrocytes, including numerous genes encoding; myelin proteins. Transcriptional changes included genes required for cell adhesion, actin cytoskeleton regulation, and fatty acid and; cholesterol biosynthesis. At the O4+ stage, there was an increase in expression of a novel proline-rich transmembrane protein (Prmp). Localized to the plasma membrane, Prmp displays adhesive properties that may be important for linking the extracellular matrix to the; actin cytoskeleton. Together, our results highlight the usefulness of this discovery-driven experimental strategy to identify genes relevant; to oligodendrocyte differentiation and myelination. Experiment Overall Design: Whole brain dissociates were prepared from one litter of 10 male postnatal day 7 rat pups for each of the 5 A2B5 bioligcal replicates and the 4 O4+ bioligical replicates. Total RNA was extracted from single A2B5+ and single O4+ cells sorted directly from postnatal day7 rat whole brain dissociates using flow cytometry.
2007-11-29 | E-GEOD-5940 | biostudies-arrayexpress
Project description:Glial progenitor cells comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for CNS remyelination, and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand-receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function. Human adult brain dissociates were sorted for one of three markers, either GLT1 (astrocyte, n =3), CD11b (microglia, n=4) or A2B5 (glial progenitor cell, n=7). In addition to positively selected, the negative fraction and unsorted dissociates were collected as matched controls for each sort.
2012-11-01 | E-GEOD-36634 | biostudies-arrayexpress
Project description:Oligodendrocytes undergo extensive changes as they differentiate from progenitors into myelinating cells. To better understand the molecular mechanisms underlying this transformation, we performed a comparative analysis using gene expression profiling of A2B5+ oligodendrocyte progenitors and O4+ oligodendrocytes. Cells were sort-purified ex vivo from postnatal rat brain using flow cytometry. Using Affymetrix microarrays, 1707 transcripts were identified with a more than twofold increase in expression inO4+oligodendrocytes. Many genes required for oligodendrocyte differentiation were upregulated in O4+ oligodendrocytes, including numerous genes encoding myelin proteins. Transcriptional changes included genes required for cell adhesion, actin cytoskeleton regulation, and fatty acid and cholesterol biosynthesis. At the O4+ stage, there was an increase in expression of a novel proline-rich transmembrane protein (Prmp). Localized to the plasma membrane, Prmp displays adhesive properties that may be important for linking the extracellular matrix to the actin cytoskeleton. Together, our results highlight the usefulness of this discovery-driven experimental strategy to identify genes relevant to oligodendrocyte differentiation and myelination. Keywords: develepmental stage, oligodendrocyte differentiation
2006-09-30 | GSE5940 | GEO
Project description:Increasing evidence indicates heterogeneity in functional and molecular properties of oligodendrocyte lineage cells both during development and under pathologic conditions. In multiple sclerosis, remyelination of grey matter lesions exceeds that in white matter. Here we used cells derived from grey matter versus white matter regions of surgically resected human brain tissue samples, to compare the capacities of human A2B5-positive progenitor cells and mature oligodendrocytes to ensheath synthetic nanofibers, and relate differences to the molecular profiles of these cells. For both cell types, the percentage of ensheathing cells was greater for grey matter versus white matter cells. For both grey matter and white matter samples, the percentage of cells ensheathing nanofibers was greater for A2B5-positive cells versus mature oligodendrocytes. Grey matter A2B5-positive cells were more susceptible than white matter A2B5-positive cells to injury induced by metabolic insults. Bulk RNA sequencing indicated that separation by cell type (A2B5-positive vs mature oligodendrocytes) is more significant than by region but segregation for each cell type by region is apparent. Molecular features of grey matter versus white matter derived A2B5-positive and mature oligodendrocytes were lower expression of mature oligodendrocyte genes and increased expression of early oligodendrocyte lineage genes. Genes and pathways with increased expression in grey matter derived cells with relevance for myelination included those related to responses to external environment, cell-cell communication, cell migration, and cell adhesion. Immune and cell death related genes were up-regulated in grey matter derived cells. We observed a significant number of up-regulated genes shared between the stress/injury and myelination processes, providing a basis for these features. In contrast to oligodendrocyte lineage cells, no functional or molecular heterogeneity was detected in microglia maintained in vitro, likely reflecting the plasticity of these cells ex vivo. The combined functional and molecular data indicate that grey matter human oligodendrocytes have increased intrinsic capacity to myelinate but also increased injury susceptibility, in part reflecting their being at a stage earlier in the oligodendrocyte lineage.
2024-11-08 | GSE281006 | GEO