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

0489475 - ÚEM 2019 RIV US eng J - Článek v odborném periodiku
Valný, Martin - Honsa, Pavel - Waloschková, Eliška - Matušková, Hana - Kriška, Ján - Kirdajová, Denisa - Androvič, Peter - Valihrach, Lukáš - Kubista, Mikael - Anděrová, Miroslava
A single-cell analysis reveals multiple roles of oligodendroglial lineage cells during post-ischemic regeneration.
Glia. Roč. 66, č. 5 (2018), s. 1068-1081. ISSN 0894-1491. E-ISSN 1098-1136
Grant CEP: GA ČR(CZ) GA17-04034S; GA ČR(CZ) GA15-04034S; GA MŠMT(CZ) ED1.1.00/02.0109
Institucionální podpora: RVO:68378041
Klíčová slova: Alzheimer's * astrocytes * cerebral ischemia
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 5.829, rok: 2018

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 and in Alzheimer disease using transgenic mice, which enable 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. To shed light on the changes in the expression patterns caused by ischemic injury, 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 ischemia: proliferative, astrocyte 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 EdU labeling to reveal that NG2 cells can differentiate directly into reactive astrocytes without preceding proliferation. In contrast, in Alzheimers-like pathology we failed to identify above listed 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 Alzheimers-like pathology, NG2 cells acquire a multipotent phenotype following ischemic injury.
Trvalý link: http://hdl.handle.net/11104/0283888