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Article ; Online: Features, Fates, and Functions of Oligodendrocyte Precursor Cells.

Hill, Robert A / Nishiyama, Akiko / Hughes, Ethan G

Cold Spring Harbor perspectives in biology

2024 Volume 16, Issue 3

Abstract: Oligodendrocyte precursor cells (OPCs) are a central nervous system resident population of glia with a distinct molecular identity and an ever-increasing list of functions. OPCs generate oligodendrocytes throughout development and across the life span in ...

Abstract	Oligodendrocyte precursor cells (OPCs) are a central nervous system resident population of glia with a distinct molecular identity and an ever-increasing list of functions. OPCs generate oligodendrocytes throughout development and across the life span in most regions of the brain and spinal cord. This process involves a complex coordination of molecular checkpoints and biophysical cues from the environment that initiate the differentiation and integration of new oligodendrocytes that synthesize myelin sheaths on axons. Outside of their progenitor role, OPCs have been proposed to play other functions including the modulation of axonal and synaptic development and the participation in bidirectional signaling with neurons and other glia. Here, we review OPC identity and known functions and discuss recent findings implying other roles for these glial cells in brain physiology and pathology.
MeSH term(s)	Oligodendrocyte Precursor Cells ; Myelin Sheath/physiology ; Oligodendroglia/physiology ; Axons/physiology ; Neurons/physiology
Language	English
Publishing date	2024-03-01
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1943-0264
ISSN (online)	1943-0264
DOI	10.1101/cshperspect.a041425
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Article: Presentation and integration of multiple signals that modulate oligodendrocyte lineage progression and myelination.

Fekete, Christopher D / Nishiyama, Akiko

Frontiers in cellular neuroscience

2022 Volume 16, Page(s) 1041853

Abstract: Myelination is critical for fast saltatory conduction of action potentials. Recent studies have revealed that myelin is not a static structure as previously considered but continues to be made and remodeled throughout adulthood in tune with the network ... ...

Abstract	Myelination is critical for fast saltatory conduction of action potentials. Recent studies have revealed that myelin is not a static structure as previously considered but continues to be made and remodeled throughout adulthood in tune with the network requirement. Synthesis of new myelin requires turning on the switch in oligodendrocytes (OL) to initiate the myelination program that includes synthesis and transport of macromolecules needed for myelin production as well as the metabolic and other cellular functions needed to support this process. A significant amount of information is available regarding the individual intrinsic and extrinsic signals that promote OL commitment, expansion, terminal differentiation, and myelination. However, it is less clear how these signals are made available to OL lineage cells when needed, and how multiple signals are integrated to generate the correct amount of myelin that is needed in a given neural network state. Here we review the pleiotropic effects of some of the extracellular signals that affect myelination and discuss the cellular processes used by the source cells that contribute to the variation in the temporal and spatial availability of the signals, and how the recipient OL lineage cells might integrate the multiple signals presented to them in a manner dialed to the strength of the input.
Language	English
Publishing date	2022-11-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2022.1041853
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Article ; Online: A new era for myelin research in Neurofibromatosis type 1.

de Blank, Peter / Nishiyama, Akiko / López-Juárez, Alejandro

Glia

2023 Volume 71, Issue 12, Page(s) 2701–2719

Abstract: Evidence for myelin regulating higher-order brain function and disease is rapidly accumulating; however, defining cellular/molecular mechanisms remains challenging partially due to the dynamic brain physiology involving deep changes during development, ... ...

Abstract	Evidence for myelin regulating higher-order brain function and disease is rapidly accumulating; however, defining cellular/molecular mechanisms remains challenging partially due to the dynamic brain physiology involving deep changes during development, aging, and in response to learning and disease. Furthermore, as the etiology of most neurological conditions remains obscure, most research models focus on mimicking symptoms, which limits understanding of their molecular onset and progression. Studying diseases caused by single gene mutations represents an opportunity to understand brain dys/function, including those regulated by myelin. Here, we discuss known and potential repercussions of abnormal central myelin on the neuropathophysiology of Neurofibromatosis Type 1 (NF1). Most patients with this monogenic disease present with neurological symptoms diverse in kind, severity, and onset/decline, including learning disabilities, autism spectrum disorders, attention deficit and hyperactivity disorder, motor coordination issues, and increased risk for depression and dementia. Coincidentally, most NF1 patients show diverse white matter/myelin abnormalities. Although myelin-behavior links were proposed decades ago, no solid data can prove or refute this idea yet. A recent upsurge in myelin biology understanding and research/therapeutic tools provides opportunities to address this debate. As precision medicine moves forward, an integrative understanding of all cell types disrupted in neurological conditions becomes a priority. Hence, this review aims to serve as a bridge between fundamental cellular/molecular myelin biology and clinical research in NF1.
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639414-0
ISSN	1098-1136 ; 0894-1491
ISSN (online)	1098-1136
ISSN	0894-1491
DOI	10.1002/glia.24432
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Article ; Online: Neonatal Brains Exhibit Higher Neural Reparative Activities than Adult Brains in a Mouse Model of Ischemic Stroke.

Nishiyama, Ryo / Nakagomi, Takayuki / Nakano-Doi, Akiko / Kuramoto, Yoji / Tsuji, Masahiro / Yoshimura, Shinichi

Cells

2024 Volume 13, Issue 6

Abstract: The neonatal brain is substantially more resistant to various forms of injury than the mature brain. For instance, the prognosis following ischemic stroke is generally poor in the elderly but favorable in neonates. Identifying the cellular and molecular ... ...

Abstract	The neonatal brain is substantially more resistant to various forms of injury than the mature brain. For instance, the prognosis following ischemic stroke is generally poor in the elderly but favorable in neonates. Identifying the cellular and molecular mechanisms underlying reparative activities in the neonatal brain after ischemic injury may provide feasible targets for therapeutic interventions in adults. To this end, we compared the reparative activities in postnatal day 13 and adult (8-12-week-old) mouse brain following middle cerebral artery occlusion. Immunohistochemistry revealed considerably greater generation of ischemia-induced neural stem/progenitor cells (iNSPCs) expressing nestin or Sox2 in ischemic areas of the neonatal brain. The iNSPCs isolated from the neonatal brain also demonstrated greater proliferative activity than those isolated from adult mice. In addition, genes associated with neuronal differentiation were enriched in iNSPCs isolated from the neonatal brain according to microarray and gene ontogeny analyses. Immunohistochemistry further revealed considerably greater production of newborn doublecortin
MeSH term(s)	Humans ; Animals ; Mice ; Aged ; Ischemic Stroke ; Brain ; Stroke ; Neural Stem Cells ; Infarction, Middle Cerebral Artery
Language	English
Publishing date	2024-03-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13060519
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Article ; Online: Cleavage of VAMP2/3 Affects Oligodendrocyte Lineage Development in the Developing Mouse Spinal Cord.

Fekete, Christopher D / Horning, Robert Z / Doron, Matan S / Nishiyama, Akiko

The Journal of neuroscience : the official journal of the Society for Neuroscience

2023 Volume 43, Issue 39, Page(s) 6592–6608

Abstract: In the developing and adult CNS, new oligodendrocytes (OLs) are generated from a population of cells known as oligodendrocyte precursor cells (OPCs). As they begin to differentiate, OPCs undergo a series of highly regulated changes to morphology, gene ... ...

Abstract	In the developing and adult CNS, new oligodendrocytes (OLs) are generated from a population of cells known as oligodendrocyte precursor cells (OPCs). As they begin to differentiate, OPCs undergo a series of highly regulated changes to morphology, gene expression, and membrane organization. This stage represents a critical bottleneck in oligodendrogliogenesis, and the regulatory program that guides it is still not fully understood. Here, we show that
MeSH term(s)	Mice ; Male ; Female ; Animals ; Vesicle-Associated Membrane Protein 2 ; Cell Lineage ; Mice, Transgenic ; Myelin Sheath/metabolism ; Oligodendroglia/metabolism ; White Matter/metabolism ; Cell Differentiation/physiology ; Spinal Cord/metabolism
Chemical Substances	Vesicle-Associated Membrane Protein 2
Language	English
Publishing date	2023-08-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.2206-21.2023
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Article ; Online: Introduction to the Special Issue on The oligodendrocyte niche in development and repair.

Colognato, Holly / Nishiyama, Akiko

Neuroscience letters

2020 Volume 730, Page(s) 134957

MeSH term(s)	Animals ; Cell Differentiation/physiology ; Cell Lineage/physiology ; Humans ; Oligodendrocyte Precursor Cells/cytology ; Oligodendroglia/cytology ; Research
Language	English
Publishing date	2020-05-01
Publishing country	Ireland
Document type	Editorial ; Introductory Journal Article
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2020.134957
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Zs.A 1166: Show issues

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Article: Shaping of Regional Differences in Oligodendrocyte Dynamics by Regional Heterogeneity of the Pericellular Microenvironment.

Sherafat, Amin / Pfeiffer, Friederike / Nishiyama, Akiko

Frontiers in cellular neuroscience

2021 Volume 15, Page(s) 721376

Abstract: Oligodendrocyte precursor cells (OPCs) are glial cells that differentiate into mature oligodendrocytes (OLs) to generate new myelin sheaths. While OPCs are distributed uniformly throughout the gray and white matter in the developing and adult brain, ... ...

Abstract	Oligodendrocyte precursor cells (OPCs) are glial cells that differentiate into mature oligodendrocytes (OLs) to generate new myelin sheaths. While OPCs are distributed uniformly throughout the gray and white matter in the developing and adult brain, those in white matter proliferate and differentiate into oligodendrocytes at a greater rate than those in gray matter. There is currently lack of evidence to suggest that OPCs comprise genetically and transcriptionally distinct subtypes. Rather, the emerging view is that they exist in different cell and functional states, depending on their location and age. Contrary to the normal brain, demyelinated lesions in the gray matter of multiple sclerosis brains contain more OPCs and OLs and are remyelinated more robustly than those in white matter. The differences in the dynamic behavior of OL lineage cells are likely to be influenced by their microenvironment. There are regional differences in astrocytes, microglia, the vasculature, and the composition of the extracellular matrix (ECM). We will discuss how the regional differences in these elements surrounding OPCs might shape their phenotypic variability in normal and demyelinated states.
Language	English
Publishing date	2021-10-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2021.721376
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Article ; Online: Many roles for oligodendrocyte precursor cells in physiology and pathology.

Nishiyama, Akiko / Serwanski, David R / Pfeiffer, Friederike

Neuropathology : official journal of the Japanese Society of Neuropathology

2021 Volume 41, Issue 3, Page(s) 161–173

Abstract: Oligodendrocyte precursor cells (OPCs) are a fourth resident glial cell population in the mammalian central nervous system. They are evenly distributed throughout the gray and white matter and continue to proliferate and generate new oligodendrocytes ( ... ...

Abstract	Oligodendrocyte precursor cells (OPCs) are a fourth resident glial cell population in the mammalian central nervous system. They are evenly distributed throughout the gray and white matter and continue to proliferate and generate new oligodendrocytes (OLs) throughout life. They were understudied until a few decades ago when immunolabeling for NG2 and platelet-derived growth factor receptor alpha revealed cells that are distinct from mature OLs, astrocytes, neurons, and microglia. In this review, we provide a summary of the known properties of OPCs with some historical background, followed by highlights from recent studies that suggest new roles for OPCs in certain pathological conditions.
MeSH term(s)	Animals ; Antigens/analysis ; Antigens/metabolism ; Cell Differentiation/physiology ; Cell Proliferation/physiology ; Glioma/genetics ; Humans ; Microscopy, Electron ; Neurons ; Oligodendrocyte Precursor Cells/metabolism ; Oligodendrocyte Precursor Cells/pathology ; Oligodendrocyte Precursor Cells/physiology ; Oligodendrocyte Precursor Cells/ultrastructure ; Oligodendroglia/physiology ; Proteoglycans/analysis ; Proteoglycans/metabolism ; Signal Transduction/genetics ; Signal Transduction/physiology
Chemical Substances	Antigens ; Proteoglycans ; chondroitin sulfate proteoglycan 4
Language	English
Publishing date	2021-04-28
Publishing country	Australia
Document type	Lecture
ZDB-ID	1483794-8
ISSN	1440-1789 ; 0919-6544
ISSN (online)	1440-1789
ISSN	0919-6544
DOI	10.1111/neup.12732
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Zs.A 5086: Show issues

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Article ; Online: The Impact of Fixation on the Detection of Oligodendrocyte Precursor Cell Morphology and Vascular Associations.

Pfeiffer, Friederike / Sherafat, Amin / Nishiyama, Akiko

Cells

2021 Volume 10, Issue 6

Abstract: Oligodendrocyte precursor cells (OPCs) display numerous protrusions that extend into the surrounding parenchyma in the brain. Depending on the preparation of the tissue analyzed, these protrusions are more or less visible. We applied six different ... ...

Abstract	Oligodendrocyte precursor cells (OPCs) display numerous protrusions that extend into the surrounding parenchyma in the brain. Depending on the preparation of the tissue analyzed, these protrusions are more or less visible. We applied six different fixation methods and compared the effect of prolonged and stronger fixation on fluorescence intensity of platelet-derived growth factor receptor alpha, a surface marker of OPCs. Importantly, the fluorescence signal is mostly lost on protrusions as compared to the cell body, which has to be considered for specific analyses. Additionally, we show numerous contacts established between OPCs and the brain vasculature, which will contribute to the understanding of the interactions between these two elements.
MeSH term(s)	Animals ; Brain/blood supply ; Cell Differentiation ; Cerebrovascular Circulation ; Mice ; Microscopy, Fluorescence ; Oligodendrocyte Precursor Cells/cytology ; Oligodendrocyte Precursor Cells/metabolism ; Tissue Fixation
Language	English
Publishing date	2021-05-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10061302
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Article ; Online: Incidence, etiology, and outcome of hospital-acquired pneumonia in patients with acute exacerbation of fibrotic idiopathic interstitial pneumonia.

Yamazaki, Ryo / Nishiyama, Osamu / Yosikawa, Kazuya / Gose, Kyuya / Oomori, Takashi / Nishikawa, Yusaku / Sano, Akiko / Matsumoto, Hisako

Respiratory investigation

2024 Volume 62, Issue 3, Page(s) 488–493

Abstract: Background: Acute exacerbations (AEs) of fibrotic idiopathic interstitial pneumonia (fIIP) that require hospitalization occur in some patients. During hospitalization, these patients can develop hospital-acquired pneumonia (HAP), a common hospital- ... ...

Abstract	Background: Acute exacerbations (AEs) of fibrotic idiopathic interstitial pneumonia (fIIP) that require hospitalization occur in some patients. During hospitalization, these patients can develop hospital-acquired pneumonia (HAP), a common hospital-acquired infection with a high mortality rate. However, the characteristics of HAP in AE-fIIP remain unknown. The purpose of this study was to determine the incidence, causative pathogens, and outcomes of HAP in patients with AE-fIIP. Methods: The medical records of consecutive patients who were hospitalized with AE-fIIP from January 2008 to December 2019 were analyzed for the incidence, causative pathogen, and survival of HAP. The records of patients with an obvious infection-triggered AE were excluded from analysis. Results: There were 128 patients with AE-fIIP (89 with idiopathic pulmonary fibrosis [IPF] and 39 with non-IPF fIIP) who were hospitalized a total of 155 times (111 with IPF and 44 with non-IPF fIIP). HAP occurred in 49 patients (40 with IPF and 9 with non-IPF fIIP). The incidence and the in-hospital mortality rates of HAP in patients with AE-fIIP were high, at 32.2% and 48.9%, respectively. Corynebacterium spp. was the most common causative pathogen, which was followed by human cytomegalovirus (HCMV). Conclusions: The incidence and the in-hospital mortality rates of HAP in patients with AE-fIIP are high. To improve their survival, patients with fIIP who had AEs and HAP should receive prompt empirical treatment for possible infections with Corynebacterium spp. and testing for HCMV.
MeSH term(s)	Humans ; Incidence ; Idiopathic Interstitial Pneumonias/therapy ; Idiopathic Pulmonary Fibrosis ; Hamman-Rich Syndrome ; Lung Diseases, Interstitial/epidemiology ; Lung Diseases, Interstitial/etiology ; Pneumonia ; Hospitals ; Disease Progression ; Retrospective Studies
Language	English
Publishing date	2024-04-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2660821-2
ISSN	2212-5353 ; 2212-5345
ISSN (online)	2212-5353
ISSN	2212-5345
DOI	10.1016/j.resinv.2024.03.008
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