In the mouse cortex, oligodendrocytes regain a plastic capacity, transforming into astrocytes after acute injury

Bai, Xianshu; Zhao, Na; Koupourtidou, Christina; Fang, Li‐Pao; Schwarz, Veronika; Caudal, Laura C.; Zhao, Renping; Hirrlinger, Johannes; Walz, Wolfgang; Bian, Shan; Huang, Wenhui; Ninkovic, Jovica; Kirchhoff, Frank; Scheller, Anja

doi:10.1016/j.devcel.2023.04.016

Cited by 18 publications

(11 citation statements)

References 81 publications

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“…give rise to GFAP + progenitor cells. This discovery highlights the inherent plasticity of the oligodendroglial lineage (Bai et al, 2023).…”

Section: Discussionmentioning

confidence: 73%

Astrocyte‐like subpopulation of NG2 glia in the adult mouse cortex exhibits characteristics of neural progenitor cells

Janeckova,

Knotek,

Kriska

et al. 2023

Glia

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Glial cells expressing neuron‐glial antigen 2 (NG2), also known as oligodendrocyte progenitor cells (OPCs), play a critical role in maintaining brain health. However, their ability to differentiate after ischemic injury is poorly understood. The aim of this study was to investigate the properties and functions of NG2 glia in the ischemic brain. Using transgenic mice, we selectively labeled NG2‐expressing cells and their progeny in both healthy brain and after focal cerebral ischemia (FCI). Using single‐cell RNA sequencing, we classified the labeled glial cells into five distinct subpopulations based on their gene expression patterns. Additionally, we examined the membrane properties of these cells using the patch‐clamp technique. Of the identified subpopulations, three were identified as OPCs, whereas the fourth subpopulation had characteristics indicative of cells likely to develop into oligodendrocytes. The fifth subpopulation of NG2 glia showed astrocytic markers and had similarities to neural progenitor cells. Interestingly, this subpopulation was present in both healthy and post‐ischemic tissue; however, its gene expression profile changed after ischemia, with increased numbers of genes related to neurogenesis. Immunohistochemical analysis confirmed the temporal expression of neurogenic genes and showed an increased presence of NG2 cells positive for Purkinje cell protein‐4 at the periphery of the ischemic lesion 12 days after FCI, as well as NeuN‐positive NG2 cells 28 and 60 days after injury. These results suggest the potential development of neuron‐like cells arising from NG2 glia in the ischemic tissue. Our study provides insights into the plasticity of NG2 glia and their capacity for neurogenesis after stroke.

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“…give rise to GFAP + progenitor cells. This discovery highlights the inherent plasticity of the oligodendroglial lineage (Bai et al, 2023).…”

Section: Discussionmentioning

confidence: 73%

Astrocyte‐like subpopulation of NG2 glia in the adult mouse cortex exhibits characteristics of neural progenitor cells

Janeckova,

Knotek,

Kriska

et al. 2023

Glia

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“…More recently it was also shown that bona fide mature oligodendrocytes can dedifferentiate via a hybrid “AO cell” state into astrocytes in vivo , in the days to weeks following traumatic and ischemic brain injury [7]. This phenotypic switch was causally linked to IL6 signalling.…”

Section: Discussionmentioning

confidence: 99%

Single nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke

Bormann,

Knoflach,

Poreba

et al. 2023

Preprint

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Reactive neuroglia critically shape the brain’s response to ischemic stroke. However, their phenotypic heterogeneity impedes a holistic understanding of the cellular composition and microenvironment of the early ischemic lesion. Here we generated a single cell resolution transcriptomics dataset of the injured brain during the acute recovery from permanent middle cerebral artery occlusion. This approach unveiled infarction and subtype specific molecular signatures in oligodendrocyte lineage cells and astrocytes, which ranged among the most transcriptionally perturbed cell types in our dataset. Specifically, we characterized and compared infarction restricted proliferating oligodendrocyte precursor cells (OPCs), mature oligodendrocytes and heterogeneous reactive astrocyte populations. Our analyses unveiled unexpected commonalities in the transcriptional response of oligodendrocyte lineage cells and astrocytes to ischemic injury. Moreover, OPCs and reactive astrocytes were involved in a shared immuno-glial cross talk with stroke specific myeloid cells.In situ,osteopontin positive myeloid cells accumulated in close proximity to proliferating OPCs and reactive astrocytes, which expressed the osteopontin receptor CD44, within the perilesional zone specifically.In vitro,osteopontin increased the migratory capacity of OPCs. Collectively, our study highlights molecular cross talk events which might govern the cellular composition and microenvironment of infarcted brain tissue in the early stages of recovery.

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“…[89][90][91] For example, Bai et al observed the transformation of oligodendrocytes into astrocytes during the AO cell stage following acute brain injury. 92 Moreover, it has also been observed that IL-6 induces oligodendrocytes to form AO cells, and LIF and BMP4 may subsequently affect astrocyte-specific differentiation. [93][94][95][96][97]…”

Section: Oligo Den Dro C Y Te Smentioning

confidence: 99%

Perspective from single‐cell sequencing: Is inflammation in acute ischemic stroke beneficial or detrimental?

Deng,

Hu,

Zhou

et al. 2023

CNS Neurosci Ther

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BackgroundAcute ischemic stroke (AIS) is a common cerebrovascular event associated with high incidence, disability, and poor prognosis. Studies have shown that various cell types, including microglia, astrocytes, oligodendrocytes, neurons, and neutrophils, play complex roles in the early stages of AIS and significantly affect its prognosis. Thus, a comprehensive understanding of the mechanisms of action of these cells will be beneficial for improving stroke prognosis. With the rapid development of single‐cell sequencing technology, researchers have explored the pathophysiological mechanisms underlying AIS at the single‐cell level.MethodWe systematically summarize the latest research on single‐cell sequencing in AIS.ResultIn this review, we summarize the phenotypes and functions of microglia, astrocytes, oligodendrocytes, neurons, neutrophils, monocytes, and lymphocytes, as well as their respective subtypes, at different time points following AIS. In particular, we focused on the crosstalk between microglia and astrocytes, oligodendrocytes, and neurons. Our findings reveal diverse and sometimes opposing roles within the same cell type, with the possibility of interconversion between different subclusters.ConclusionThis review offers a pioneering exploration of the functions of various glial cells and cell subclusters after AIS, shedding light on their regulatory mechanisms that facilitate the transformation of detrimental cell subclusters towards those that are beneficial for improving the prognosis of AIS. This approach has the potential to advance the discovery of new specific targets and the development of drugs, thus representing a significant breakthrough in addressing the challenges in AIS treatment.

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In the mouse cortex, oligodendrocytes regain a plastic capacity, transforming into astrocytes after acute injury

Cited by 18 publications

References 81 publications

Astrocyte‐like subpopulation of NG2 glia in the adult mouse cortex exhibits characteristics of neural progenitor cells

Astrocyte‐like subpopulation of NG2 glia in the adult mouse cortex exhibits characteristics of neural progenitor cells

Single nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke

Perspective from single‐cell sequencing: Is inflammation in acute ischemic stroke beneficial or detrimental?

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