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Single cell approaches define two mammalian oligodendrocyte precursor cell populations and their evolution over developmental time [Xenium In Situ Gene Expression]

ABSTRACT: Here, we have used single-cell RNA sequencing (scRNA-seq), single-cell ATAC sequencing (scATAC-seq) and spatial transcriptomics to characterize murine cortical OPCs throughout postnatal life. During development, we identify two differentially-localized PDGFRα-positive OPC populations that are transcriptionally and epigenetically distinct. One population (active or actOPCs) is metabolically active and is enriched in white matter. The second (homeostatic or hOPCs) is less active, enriched in grey matter, and predicted to derive from actOPCs. In adulthood, these two groups are transcriptionally but not epigenetically distinct, and relative to developing OPCs are less active metabolically with much less open chromatin. When adult oligodendrogenesis is enhanced following experimental demyelination, adult OPCs do not reacquire a developmental open chromatin state, and the oligodendrogenesis trajectory is distinct from that seen neonatally. These data support a model where two OPC populations subserve distinct postnatal functions, and where neonatal and adult OPC-mediated oligodendrogenesis are fundamentally different.

ORGANISM(S): Mus musculus

PROVIDER: GSE255407 | GEO | 2024/03/05

REPOSITORIES: GEO

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Single cell approaches define two mammalian oligodendrocyte precursor cell populations and their evolution over developmental time [scMultiome-seq]

Project description:Here, we have used single-cell RNA sequencing (scRNA-seq), single-cell ATAC sequencing (scATAC-seq) and spatial transcriptomics to characterize murine cortical OPCs throughout postnatal life. During development, we identify two differentially-localized PDGFRα-positive OPC populations that are transcriptionally and epigenetically distinct. One population (active or actOPCs) is metabolically active and is enriched in white matter. The second (homeostatic or hOPCs) is less active, enriched in grey matter, and predicted to derive from actOPCs. In adulthood, these two groups are transcriptionally but not epigenetically distinct, and relative to developing OPCs are less active metabolically with much less open chromatin. When adult oligodendrogenesis is enhanced following experimental demyelination, adult OPCs do not reacquire a developmental open chromatin state, and the oligodendrogenesis trajectory is distinct from that seen neonatally. These data support a model where two OPC populations subserve distinct postnatal functions, and where neonatal and adult OPC-mediated oligodendrogenesis are fundamentally different.

2024-03-05 | GSE255406 | GEO

Single cell approaches define two mammalian oligodendrocyte precursor cell populations and their evolution over developmental time [scRNA-seq]

2024-03-05 | GSE255405 | GEO

Single cell approaches define two mammalian oligodendrocyte precursor cell populations and their evolution over developmental time [scATAC-seq]

2024-03-05 | GSE255404 | GEO

Oligodendrocyte Progenitor Cell Transcriptome in White Matter Stroke

Project description:Tissue progenitors maintain the integrity of organ systems through aging and stress. The brain’s white matter regions experience ischemic lesions and age-dependent degeneration. Brain white matter contains progenitors, oligodendrocyte precursor cells (OPCs), which can repair some insults. The response of OPCs to white matter ischemia and aging is not known. We characterized the response of OPCs to white matter stroke using OPC reporter mice, cell migration tracking, OPC specific RNA sequencing, and mechanistic studies in candidate biochemical pathways in the aged brain. White matter stroke induces initial proliferation of local OPCs but blocks differentiation, shunting a portion into astrocytes. Candidate signaling pathways for this differentiation block including novel interactions of inhibin and matrilin-2 and new roles of NgR1 ligands following white matter stroke. Stroke induces inhibin expression in astrocytes and downregulates OPC matrilin-2 that contributes into OPC differentiation block. Antagonism of NgR1 ligands promotes OPC differentiation by attenuating the OPC astrocytic transformation and enhances functional recovery from stroke in aged animals.

2019-11-15 | GSE53737 | GEO

Single-cell sequencing of PDGFRα-expressing cells in the adult mouse brain.

Project description:Oligodendrocyte progenitor cells (OPCs) are a mitotically active population of glia that comprise approximately 5% of the adult brain. OPCs maintain their proliferative capacity and ability to differentiate in oligodendrocytes throughout adulthood, but relatively few mature oligodendrocytes are produced following developmental myelination. Recent work has begun to demonstrate that OPCs likely perform multiple functions in both homeostasis and disease, and can significantly impact behavioral phenotypes such as food intake and depressive symptoms. However, the exact mechanisms through which OPCs might influence brain function remains unclear. In this work, we demonstrate that OPCs are transcriptionally diverse and separate into three distinct populations in the homeostatic brain. These three groups show distinct transcriptional signatures and enrichment of biological processes unique to individual OPC populations. We have validated these OPC populations using multiple methods, including multiplex RNA in situ hybridization and RNA flow cytometry. This study provides an important resource that profiles the transcriptome of adult OPCs and will provide a significant foundation for further investigation into novel OPC functions.

2020-03-17 | GSE147075 | GEO

Changes in the oligodendrocyte cell progenitor cell proteome with ageing

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

Changes in the oligodendrocyte cell progenitor cell proteome with ageing

2020-05-22 | PXD013708 | Pride

Primary cilia control Oligodendrocyte Precursor Cell proliferation in white matter injury via Hedgehog-independent CREB signaling.

Project description:Remyelination after white matter injury (WMI) often fails in diseases such as multiple sclerosis due to improper recruitment and repopulation of oligodendrocyte precursor cells (OPCs) in lesions. How OPCs elicit specific intracellular programs in response to a chemically and mechanically diverse environment to properly regenerate myelin remains unclear. OPCs construct primary cilia, specialized signaling compartments that transduce Hh and GPCR signals. We investigated the role of primary cilia in the OPC response to WMI. Removing cilia from OPCs genetically via deletion of Ift88 results in OPCs failing to repopulate WMI lesions due to reduced proliferation. Interestingly, loss of cilia does not affect Hh signaling in OPCs or their responsiveness to Hh signals, but instead leads to dysfunctional cAMP-dependent CREB-mediated transcription. As inhibition of CREB activity in OPCs reduces proliferation, we propose that a GPCR/cAMP/CREB signaling axis initiated at OPC cilia orchestrates OPC proliferation during development and in response to WMI.

2023-09-29 | GSE243997 | GEO

Endothelin-1-Endothelin B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury

Project description:Preterm cerebral white matter injury (WMI), a major form of prenatal brain injury, may potentially be treated by oligodendrocyte (OL) precursor cell (OPC) transplantation. However, the defective differentiation of OPCs during WMI seriously hampers the clinical application of OPC transplantation. Thus, improving the ability of transplanted OPCs to differentiate is critical to OPC transplantation therapy for WMI. Here, we established a hypoxia-ischemia-induced preterm WMI model in mice and screened the molecules affected by WMI using single-cell RNA sequencing. We revealed that endothelin (ET)-1 and endothelin receptor B (ETB) were a pair of signaling molecules for the interaction between neurons and OPCs, and that preterm WMI led to an increase in the number of ETB-positive OPCs and premyelinating OLs. Furthermore, the maturation of OLs was reduced by knocking out ETB, but promoted by stimulating ET-1/ETB signaling. Our work reveals a new signaling module for neuron-OPC interaction and provides new insight for therapy targeting preterm WMI.

2023-03-04 | GSE225580 | GEO

Functionally distinct subgroups of Oligodendrocyte precursor cells integrate neural activity and execute myelin formation

Project description:Neuronal activity can regulate the formation of new myelin by controlling division and differentiation of oligodendrocyte precursor cells (OPCs). If activity directly instructs OPCs to differentiate or whether this process underlies a more complex regulation in unclear, because it is not known if OPCs with different functions exist. By following lineage formation of individual OPC clones, single cell RNA sequencing, in vivo calcium imaging and manipulation of neural activity, we show that OPCs in the zebrafish spinal cord can be divided into two functional entities. One subgroup forms elaborate process networks and exhibits a high degree of calcium signalling activity, but infrequently differentiates, despite contact with permissive axons. Instead, these OPCs can divide in an activity and calcium dependent manner to produce another subgroup of OPCs, which readily differentiates and which shows less elaborate, more dynamic processes, and less calcium signaling activity. Our data reveal functional diversity within the OPC population in responding to neural activity and show that activity regulates proliferation of a subset of OPCs that is distinct from the cells that will differentiate, with implications for myelin development, plasticity, and repair.

2020-02-18 | GSE132166 | GEO

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