Single-Cell RNA-seq study of E13.5 and P7 brain and Spinal Cord Pdgfra-GFP positive samples during development in Mice.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE95194 | GEO | 2018/08/02
REPOSITORIES: GEO
Similar Datasets
Project description:Pdgfra+ oligodendrocyte precursor cells (OPCs) arise in distinct specification waves during embryo- genesis in the central nervous system (CNS). It is unclear whether there is a correlation between these waves and different oligodendrocyte (OL) states at adult stages. Here, we present bulk and single-cell transcriptomics resources providing insights on how transitions between these states occur. We found that post-natal OPCs from brain and spinal cord present similar transcriptional signatures. Moreover, post-natal OPC progeny of E13.5 Pdgfra+ cells present electrophysiological and transcriptional profiles similar to OPCs derived from subsequent specification waves, indicating that Pdgfra+ pre- OPCs rewire their transcriptional network during development. Single-cell RNA-seq and lineage tracing indicates that a subset of E13.5 Pdgfra+ cells originates cells of the pericyte lineage. Thus, our results indicate that embryonic Pdgfra+ cells in the CNS give rise to distinct post-natal cell lineages, including OPCs with convergent transcriptional profiles in different CNS regions.
2018-07-21 | GSE95093 | GEO
Project description:The mature CNS contains PDGFRA+ ‘oligodendrocyte progenitor cells’ (OPC) which may remain quiescent, proliferate, or differentiate into oligodendrocytes. In human gliomas, rapidly proliferating Olig2+ cells resembling OPCs are frequently observed. We sought to identify, in vivo, candidate pathways uniquely required for OPC differentiation or quiescence. Using the bacTRAP methodology, we generated and analyzed mouse lines for translational profiling the major cells types (including OPCs), in the normal mouse brain. We then profiled oligodendoglial (Olig2+) cells from a mouse model of Pdgf-driven glioma. This analysis confirmed that Olig2+ tumor cells are most similar to OPCs, yet, it identified differences in key progenitor genes - candidates for promotion of differentiation or quiescence. There are two datasets here. One characterizes the normal translational profiles of neurons, astrocytes, mature and immature oligodendrocytes. Each cell type was profiled in triplicate, from pools of at least two mice, and total RNA controls were collected in parallel. The second dataset includes translational profiles of Olig2 positive cells from tumors form several variations of a murine model of glioma. Each variation was collected at least in triplicate, and total RNA controls were analyzed in parallel. All translational profiles were generated using the Translating Ribosome Affinity Purification protocol.
2012-10-04 | E-GEOD-30626 | biostudies-arrayexpress
Project description:The mature CNS contains PDGFRA+ ‘oligodendrocyte progenitor cells’ (OPC) which may remain quiescent, proliferate, or differentiate into oligodendrocytes. In human gliomas, rapidly proliferating Olig2+ cells resembling OPCs are frequently observed. We sought to identify, in vivo, candidate pathways uniquely required for OPC differentiation or quiescence. Using the bacTRAP methodology, we generated and analyzed mouse lines for translational profiling the major cells types (including OPCs), in the normal mouse brain. We then profiled oligodendoglial (Olig2+) cells from a mouse model of Pdgf-driven glioma. This analysis confirmed that Olig2+ tumor cells are most similar to OPCs, yet, it identified differences in key progenitor genes - candidates for promotion of differentiation or quiescence.
2012-10-04 | GSE30626 | GEO
Project description:Epigenetic lesions that disrupt gene regulatory elements and expression are increasingly recognized as pervasive drivers of human cancers. However, we currently lack the in vitro and in vivo models required to functionally validate such lesions and their tumorigenic impact. Here we model aberrations that arise in Isocitrate Dehydrogenase mutant (IDHmut) lower-grade gliomas, which exhibit profound DNA hypermethylation. We initially focus on a CTCF insulator downstream of the PDGFRA oncogene that is recurrently disrupted in IDHmut gliomas. We demonstrate that disruption of the syntenic insulator in mouse oligodendrocyte-progenitor cells (OPCs) allows an OPC-specific enhancer to contact and induce PDGFRA, thereby increasing proliferation. In contrast, insulator disruption did not affect PDGFRA expression in neural progenitor cells (NPCs), which lack the enhancer. We also model a second recurrent epigenetic lesion in IDHmut gliomas, the methylation-dependent silencing of the CDKN2A tumor suppressor. We show that inactivation of CDKN2A/p19ARF by de novo promoter methylation or mutation drives OPC proliferation and synergizes with PDGFRA insulator loss. Finally, we use lentiviruses to coordinately inactivate the PDGFRA insulator and CDKN2A in mouse corpus callosum, resulting in low-grade gliomagenesis in vivo. Our study recapitulates recurrent epigenetic lesions in mouse models and demonstrates that combination of PDGFRA activation and CDKN2A silencing can transform OPCs in vitro and drive gliomagenesis in vivo.
2023-07-25 | GSE225793 | GEO
Project description:Epigenetic lesions that disrupt gene regulatory elements and expression are increasingly recognized as pervasive drivers of human cancers. However, we currently lack the in vitro and in vivo models required to functionally validate such lesions and their tumorigenic impact. Here we model aberrations that arise in Isocitrate Dehydrogenase mutant (IDHmut) lower-grade gliomas, which exhibit profound DNA hypermethylation. We initially focus on a CTCF insulator downstream of the PDGFRA oncogene that is recurrently disrupted in IDHmut gliomas. We demonstrate that disruption of the syntenic insulator in mouse oligodendrocyte-progenitor cells (OPCs) allows an OPC-specific enhancer to contact and induce PDGFRA, thereby increasing proliferation. In contrast, insulator disruption did not affect PDGFRA expression in neural progenitor cells (NPCs), which lack the enhancer. We also model a second recurrent epigenetic lesion in IDHmut gliomas, the methylation-dependent silencing of the CDKN2A tumor suppressor. We show that inactivation of CDKN2A/p19ARF by de novo promoter methylation or mutation drives OPC proliferation and synergizes with PDGFRA insulator loss. Finally, we use lentiviruses to coordinately inactivate the PDGFRA insulator and CDKN2A in mouse corpus callosum, resulting in low-grade gliomagenesis in vivo. Our study recapitulates recurrent epigenetic lesions in mouse models and demonstrates that combination of PDGFRA activation and CDKN2A silencing can transform OPCs in vitro and drive gliomagenesis in vivo.
2023-07-25 | GSE225732 | GEO
Project description:Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming implicating chromatin remodeling. Here, we report on uncharacterized functions of the chromatin remodelers Chd7 and Chd8 in OPCs. Their OPC-chromatin-binding profile combined with transcriptome and open-chromatin analysis of Chd7-deleted OPCs, demonstrates that Chd7 controls OPC differentiation through chromatin-opening and transcriptional activation of key regulators such as Sox10, Nkx2.2 and Gpr17. Chd7 is however dispensable for oligodendrocyte stage progression, consistent with Chd8 compensatory function, as suggested by its chromatin binding profile. Furthermore, Chd7 protects non-proliferative OPCs from apoptosis by chromatin-closing and transcriptional repression of p53. Mutations in CHD7 and CHD8 are associated with developmental disorders, such as CHARGE syndrome and autism respectively, and our results offer new avenues to understand and modulate their functions in disease.
2018-08-29 | GSE116598 | GEO
Project description:Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming implicating chromatin remodeling. Mounting evidence indicates that chromatin remodelers play important roles during normal development and their mutations are associated with neurodevelopmental defects, with CHD7 haploinsuficiency being the cause of CHARGE syndrome and CHD8 being one of the strongest Autism Spectrum Disorder (ASD) high-risk associated genes. Here, we report on uncharacterized functions of the chromatin remodelers Chd7 and Chd8 in OPCs. Their OPC-chromatin-binding profile combined with transcriptome and chromatin accessibility analyses of Chd7-deleted OPCs, demonstrates that Chd7 protects non-proliferative OPCs from apoptosis by chromatin-closing and transcriptional repression of p53. Furthermore, Chd7 controls OPC differentiation through chromatin-opening and transcriptional activation of key regulators, including Sox10, Nkx2.2 and Gpr17. Chd7 is however dispensable for oligodendrocyte stage progression, consistent with Chd8 compensatory function, as suggested by their common chromatin binding profiles and genetic interaction. Finally, CHD7 and CHD8 bind in OPCs to a majority of ASD-risk associated genes, suggesting an implication of oligodendrocyte lineage cells in ASD neurological defects. Our results thus offer new avenues to understand and modulate the CHD7 and CHD8 functions in normal development and disease.
2018-08-29 | GSE116600 | GEO
Project description:Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming implicating chromatin remodeling. Mounting evidence indicates that chromatin remodelers play important roles during normal development and their mutations are associated with neurodevelopmental defects, with CHD7 haploinsuficiency being the cause of CHARGE syndrome and CHD8 being one of the strongest Autism Spectrum Disorder (ASD) high-risk associated genes. Here, we report on uncharacterized functions of the chromatin remodelers Chd7 and Chd8 in OPCs. Their OPC-chromatin-binding profile combined with transcriptome and chromatin accessibility analyses of Chd7-deleted OPCs, demonstrates that Chd7 protects non-proliferative OPCs from apoptosis by chromatin-closing and transcriptional repression of p53. Furthermore, Chd7 controls OPC differentiation through chromatin-opening and transcriptional activation of key regulators, including Sox10, Nkx2.2 and Gpr17. Chd7 is however dispensable for oligodendrocyte stage progression, consistent with Chd8 compensatory function, as suggested by their common chromatin binding profiles and genetic interaction. Finally, CHD7 and CHD8 bind in OPCs to a majority of ASD-risk associated genes, suggesting an implication of oligodendrocyte lineage cells in ASD neurological defects. Our results thus offer new avenues to understand and modulate the CHD7 and CHD8 functions in normal development and disease.
2018-08-29 | GSE116599 | GEO
Project description:Following CNS demyelination, adult oligodendrocyte progenitor cells (OPCs) can differentiate into new myelin-forming oligodendrocytes in a regenerative process called remyelination. While remyelination is very efficient in young adults, its efficiency declines progressively with ageing. Here we performed proteomic analysis on OPCs isolated acutely from the brains of neonate, young and aged female rats. Approximately 60% of the proteins are expressed at different levels in OPCs from neonates compared to their adult counterparts. The amount of myelin-associated and cell adhesion proteins are increased with age, while cholesterol-biosynthesis, transcription factors and cell cycle proteins decreased. Our experiments provide the first ageing OPC rodent proteome, revealing the distinct features of neonatal and adult OPCs, and providing new insights into why remyelination efficiency declines with ageing and potential roles for aged OPCs in other neurodegenerative diseases.
2022-02-25 | PXD010383 | Pride
Project description:Following CNS demyelination, adult oligodendrocyte progenitor cells (OPCs) can differentiate into new myelin-forming oligodendrocytes in a regenerative process called remyelination. While remyelination is very efficient in young adults, its efficiency declines progressively with ageing. Here we performed proteomic analysis on OPCs isolated acutely from the brains of neonate, young and aged female rats. Approximately 60% of the proteins are expressed at different levels in OPCs from neonates compared to their adult counterparts. The amount of myelin-associated and cell adhesion proteins are increased with age, while cholesterol-biosynthesis, transcription factors and cell cycle proteins decreased. Our experiments provide the first ageing OPC rodent proteome, revealing the distinct features of neonatal and adult OPCs, and providing new insights into why remyelination efficiency declines with ageing and potential roles for aged OPCs in other neurodegenerative diseases.
2020-05-22 | PXD013708 | Pride