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      Cell of all trades: oligodendrocyte precursor cells in synaptic, vascular, and immune function

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          Abstract

          In this review, Akay et al. discuss the physiological roles of oligodendrocyte precursor cells (OPCs) in the brain beyond their contribution to myelination. The authors also explore how sex and age may influence OPC activity, and discuss how OPC dysfunction may play a primary role in numerous neurological and neuropsychiatric diseases.

          Abstract

          Oligodendrocyte precursor cells (OPCs) are not merely a transitory progenitor cell type, but rather a distinct and heterogeneous population of glia with various functions in the developing and adult central nervous system. In this review, we discuss the fate and function of OPCs in the brain beyond their contribution to myelination. OPCs are electrically sensitive, form synapses with neurons, support blood–brain barrier integrity, and mediate neuroinflammation. We explore how sex and age may influence OPC activity, and we review how OPC dysfunction may play a primary role in numerous neurological and neuropsychiatric diseases. Finally, we highlight areas of future research.

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          A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease.

          Hadas Keren‐Shaul, Amit Spinrad, Assaf Weiner … (2017)
          Alzheimer's disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, defining the roles of immune cell subsets in AD onset and progression has been challenging. Using transcriptional single-cell sorting, we comprehensively map all immune populations in wild-type and AD-transgenic (Tg-AD) mouse brains. We describe a novel microglia type associated with neurodegenerative diseases (DAM) and identify markers, spatial localization, and pathways associated with these cells. Immunohistochemical staining of mice and human brain slices shows DAM with intracellular/phagocytic Aβ particles. Single-cell analysis of DAM in Tg-AD and triggering receptor expressed on myeloid cells 2 (Trem2)(-/-) Tg-AD reveals that the DAM program is activated in a two-step process. Activation is initiated in a Trem2-independent manner that involves downregulation of microglia checkpoints, followed by activation of a Trem2-dependent program. This unique microglia-type has the potential to restrict neurodegeneration, which may have important implications for future treatment of AD and other neurodegenerative diseases. VIDEO ABSTRACT.
          Article 0 comments Cited 1837 times – based on 0 reviews     Review now
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            Single-cell transcriptomic analysis of Alzheimer’s disease

            Hansruedi Mathys, Jose Davila-Velderrain, Zhuyu Peng … (2019)
            Alzheimer's disease is a pervasive neurodegenerative disorder, the molecular complexity of which remains poorly understood. Here, we analysed 80,660 single-nucleus transcriptomes from the prefrontal cortex of 48 individuals with varying degrees of Alzheimer's disease pathology. Across six major brain cell types, we identified transcriptionally distinct subpopulations, including those associated with pathology and characterized by regulators of myelination, inflammation, and neuron survival. The strongest disease-associated changes appeared early in pathological progression and were highly cell-type specific, whereas genes upregulated at late stages were common across cell types and primarily involved in the global stress response. Notably, we found that female cells were overrepresented in disease-associated subpopulations, and that transcriptional responses were substantially different between sexes in several cell types, including oligodendrocytes. Overall, myelination-related processes were recurrently perturbed in multiple cell types, suggesting that myelination has a key role in Alzheimer's disease pathophysiology. Our single-cell transcriptomic resource provides a blueprint for interrogating the molecular and cellular basis of Alzheimer's disease.
            Article 0 comments Cited 982 times – based on 0 reviews     Review now
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              The serial cultivation of human diploid cell strains.

              L Hayflick, P.S. Moorhead (1961)
              Article 0 comments Cited 958 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Genes Dev
                Journal ID (iso-abbrev): Genes Dev
                Journal ID (hwp): genesdev
                Journal ID (pmc): genesdev
                Journal ID (publisher-id): GAD
                Title: Genes & Development
                Publisher: Cold Spring Harbor Laboratory Press
                ISSN (Print): 0890-9369
                ISSN (Electronic): 1549-5477
                Publication date (Print): 1 February 2021
                Volume: 35
                Issue: 3-4
                Pages: 180-198
                Affiliations
                [1 ]Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
                [2 ]Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
                Author notes
                [3]

                These authors contributed equally to this work.

                Corresponding author: lhtsai@ 123456mit.edu
                Author information
                http://orcid.org/0000-0003-1262-0592
                Article
                Medline ID: 8711660
                DOI: 10.1101/gad.344218.120
                PMC ID: 7849363
                PubMed ID: 33526585
                SO-VID: d1bd7d39-1f34-4505-a335-6bb81d1bd884
                Copyright © © 2021 Akay et al.; Published by Cold Spring Harbor Laboratory Press
                License:

                This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Page count
                Pages: 19
                Categories
                Subject: 8
                Subject: Review

                Keywords: alzheimer's disease,ng2 glia,blood–brain barrier,immunity,neurodevelopment,oligodendrocyte precursor,senescence,sex differences,synapse
                Data availability:
                Keywords: alzheimer's disease, ng2 glia, blood–brain barrier, immunity, neurodevelopment, oligodendrocyte precursor, senescence, sex differences, synapse

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