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

Valny, Martin; Honsa, Pavel; Waloschkova, Eliska LU ; Matuskova, Hana; Kriska, Jan; Kirdajova, Denisa; Androvic, Peter; Valihrach, Lukas; Kubista, Mikael and Anderova, Miroslava (2018) In GLIA 66(5). p.1068-1081
Abstract

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... (More)

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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author
publishing date
type
Contribution to journal
publication status
published
subject
in
GLIA
volume
66
issue
5
pages
14 pages
publisher
John Wiley & Sons
external identifiers
  • scopus:85041188414
ISSN
1098-1136
DOI
10.1002/glia.23301
language
English
LU publication?
no
id
f0d72950-3267-4688-8ceb-4db87a6e83f9
date added to LUP
2018-09-05 14:28:35
date last changed
2018-09-16 04:56:57
@article{f0d72950-3267-4688-8ceb-4db87a6e83f9,
  abstract     = {<p>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.</p>},
  author       = {Valny, Martin and Honsa, Pavel and Waloschkova, Eliska and Matuskova, Hana and Kriska, Jan and Kirdajova, Denisa and Androvic, Peter and Valihrach, Lukas and Kubista, Mikael and Anderova, Miroslava},
  issn         = {1098-1136},
  language     = {eng},
  number       = {5},
  pages        = {1068--1081},
  publisher    = {John Wiley & Sons},
  series       = {GLIA},
  title        = {A single-cell analysis reveals multiple roles of oligodendroglial lineage cells during post-ischemic regeneration},
  url          = {http://dx.doi.org/10.1002/glia.23301},
  volume       = {66},
  year         = {2018},
}