Multipotency and therapeutic potential of NG2 cells

Valný, Martin; Honsa, Pavel; Kriška, Ján; Andĕrová, Miroslava

doi:10.1016/j.bcp.2017.05.008

Cited by 25 publications

(26 citation statements)

References 200 publications

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“…However, their even distribution throughout the whole CNS suggests that NG2 cells possess additional functions, apart from being just progenitor cells (Hill & Nishiyama, 2014). However, numerous fate-mapping studies have confirmed NG2 cells solely as unipotent precursors of OLs in the intact adult CNS (Dimou & Gallo, 2015;Valny, Honsa, Kriska, & Anderova, 2017). Such synapses serve the neuronal regulation of NG2 cell differentiation into OLs, and disappear early after the differentiation onset (Spitzer, Volbracht, & Lundgaard, 2016).…”

Section: Introductionmentioning

confidence: 99%

A single‐cell analysis reveals multiple roles of oligodendroglial lineage cells during post‐ischemic regeneration

Valný

Honsa

Waloschková

et al. 2018

Glia

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NG2 cells represent precursors of oligodendrocytes under physiological conditions; however, following cerebral ischemia they play an important role in glial scar formation. Here, we compared the expression profiles of oligodendroglial lineage cells, after focal cerebral ischemia (FCI) and in Alzheimer's-like pathology using transgenic mice, which enables genetic fate-mapping of Cspg4-positive NG2 cells and their progeny, based on the expression of red fluorescent protein tdTomato. tdTomato-positive cells possessed the expression profile of NG2 cells and oligodendrocytes; however, based on the expression of cell type-specific genes, we were able to distinguish between them. To shed light on the changes in the expression patterns caused by FCI, we employed self-organizing Kohonen maps, enabling the division of NG2 cells and oligodendrocytes into subpopulations based on similarities in the expression profiles of individual cells. We identified three subpopulations of NG2 cells emerging after FCI: proliferative; astrocyte-like and oligodendrocyte-like NG2 cells; such phenotypes were further confirmed by immunohistochemistry. Oligodendrocytes themselves formed four subpopulations, which reflected the process of oligodendrocytes maturation. Finally, we used 5-ethynyl-2' deoxyuridine (EdU) labeling to reveal that NG2 cells can differentiate directly into reactive astrocytes without preceding proliferation. In contrast, in Alzheimer's-like pathology we failed to identify these subpopulations. Collectively, here we identified several yet unknown differences between the expression profiles of NG2 cells and oligodendrocytes, and characterized specific genes contributing to oligodendrocyte maturation and phenotypical changes of NG2 cells after FCI. Moreover, our results suggest that, unlike in Alzheimer's-like pathology, NG2 cells acquire a multipotent phenotype following FCI.

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Section: Introductionmentioning

confidence: 99%

A single‐cell analysis reveals multiple roles of oligodendroglial lineage cells during post‐ischemic regeneration

Valný

Honsa

Waloschková

et al. 2018

Glia

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“…Thus, they are the ideal cells to respond to injury and be manipulated to promote regeneration. Still, whether NG2-glia can give rise to neurons is highly debated, and if so, the underlying mechanism was unknown Falk and Gotz, 2017;Valny, et al, 2017;Vigano and Dimou, 2016). Here, using Drosophila in vivo functional genetic analysis we have identified neuronal Ia-2 and insulin signaling as the key interactors of the NG2 homologue kon, that can induce neurogenesis from NG2-like glial cells.…”

Section: Discussionmentioning

confidence: 97%

“…A critical missing link to understand how to induce CNS regeneration in non-regenerating animals such as humans, had been to identify factors that might interact with NG2 to induce regenerative neurogenesis. NG2 is key because NG2-glia are the only population of progenitor cells that are present throughout life in the adult human brain Torper, et al, 2015;Valny, et al, 2017). Thus, they are the ideal cells to respond to injury and be manipulated to promote regeneration.…”

Section: Discussionmentioning

confidence: 99%

Regenerative neurogenic response from glia requires insulin driven neuron-glia communication

Hidalgo

Harrison

Connolly

et al. 2019

Preprint

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A key goal to promote central nervous system regeneration is to discover mechanisms of injuryinduced de novo neurogenesis. Glial cells might induce neurogenesis upon injury, but this is debated, and underlying mechanisms are unknown. A critical missing link is the identification of neuronal factors that could interact with glial NG2 to facilitate regeneration. Here, we used Drosophila genetics to search for neuronal partners of the NG2 homologue Kon-tiki (Kon), and identified Ia-2, involved in insulin secretion. Ia-2 is exclusively neuronal, and alterations in Ia-2 function destabilized cell fate. Injury increased ia-2 expression and induced neural stem cells. Using glial markers, genetic epistasis analysis and lineage tracing, we demonstrate that Ia-2 functions together with Kon and

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“…Although the neurogenic potential of NG2 cells has been extensively studied (9,11), they are primarily considered as the major source of new oligodendrocytes that potentially can lead to remyelination in demyelinating disorders, like multiple sclerosis (12). Accordingly, considerable effort has been focused on the development of new strategies to potentiate their proliferation and neuronal differentiation via the manipulation of a variety of signaling molecules, growth factors, hormones and even neurotransmitters (11).…”

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confidence: 99%

The pharmacology of neurogenesis: Conceptual advances and remaining challenges

Boccazzi

Ceruti

2017

Biochemical Pharmacology

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Once the development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. In the adult centers, the nerve paths are something fixed, ended, and immutable. Everything may die, nothing may be regenerated". This "no new adult brain cells" dogma expressed by the great Spanish neuroscientist Santiago Ramón y Cajal a century ago (1). Despite challenges to the dogma in the 1960s, most of which were greeted with skepticism, it remained the prevailing view up to the 1980s when more convincing results reported the genesis of new brain cells over the entire lifespan of mammals (2). A Medline search of the term "neurogenesis" in 2017 retrieved more than 22,800 papers with an exponential increase starting from early 90s. Among them, the entry "adult neurogenesis" occurs in over 8,000 papers from the beginning of the 21 st century. These numbers underpin the growing interest in this topic and the possible therapeutic exploitation of adult neurogenesis for currently incurable brain pathologies. Some confusion may arise in the use of the term neurogenesis, since it sometimes broadly refers to the generation of both new neurons and glial cells from multipotent precursors. To avoid any misunderstandings, in the present Special Issue of Biochemical Pharmacology we refer to a second more restricted meaning, specifically the generation of new neurons from resident neural stem cells (NSCs) or multipotent progenitors (2). Two main regions in the brain show continuing neurogenesis during adult life: the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampus (3, 4). Within these two areas, NSCs undergo proliferation, asymmetric division, migration and differentiation. As

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Multipotency and therapeutic potential of NG2 cells

Cited by 25 publications

References 200 publications

A single‐cell analysis reveals multiple roles of oligodendroglial lineage cells during post‐ischemic regeneration

A single‐cell analysis reveals multiple roles of oligodendroglial lineage cells during post‐ischemic regeneration

Regenerative neurogenic response from glia requires insulin driven neuron-glia communication

The pharmacology of neurogenesis: Conceptual advances and remaining challenges

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