Effects of the transcription factor Olig1 on the differentiation and remyelination of oligodendrocyte precursor cells after focal cerebral ischemia in rats

Objectives: White matter injury aggravates neurological and cognitive impairment in experimental ischemic stroke. M2 microglia promote oligodendrocyte precursor cells survival and differentiation, and further enhance white matter repair. However, the molecular mechanism is unclear. Here, we explored the effect and mechanism of M2 microglia-derived exosomes on white matter repair after focal cerebral ischemia in mice. Methods: Microglia BV2 cells were polarized to M2 phenotype by IL-4 stimulation. Exosomes were isolated from M2 microglia (M2-Exo) and unstimulated microglia as a control (M0-Exo). M2-Exo and M0-Exo (100 μg) were intravenously injected after 90-minute middle cerebral artery occlusion in mice (n=72). Brain atrophy volume and neuro behavioral outcomes were examined in 28 days following focal cerebral ischemia. Oligodendrocyte precursor cells survival, differentiation and white matter integrity were evaluated. Exosomal miRNA and target gene were further examined to explore molecular mechanism. Results: M2-Exo treatment promoted sensorimotor and memory function recovery ( p <0.05), and further reduced brain atrophy compared to the M0-Exo control group ( p <0.001). Immunostaining showed that M2-Exo increased the number of BrdU + /Pdgfr-α + and BrdU + /adenomatous polyposis coli + cells, enhanced myelin basic protein fluorescence-intensity compared to the control ( p <0.05). M2-Exo increased oligodendrocyte precursor cell survival under OGD in vi tro , ( p <0.05) and differentiation ( p <0.05). Exosomal miRNA sequencing and PCR identified that miR-23a-5p was enriched in M2-Exo. Conclusion: Our results showed that M2-Exo treatment enhanced oligodendrocyte precursor cell survival and differentiation, further promoted white matter repair and long-term functional recovery, suggesting that M2-Exo is a novel therapeutic strategy for the white matter repair after ischemic brain injury.

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Effects of Aging on Neural Stem/Progenitor Cells and Oligodendrocyte Precursor Cells after Focal Cerebral Ischemia in Spontaneously Hypertensive Rats

Cell Transplantation ◽

10.3727/096368916x690557 ◽

2016 ◽

Vol 25 (4) ◽

pp. 705-714 ◽

Cited By ~ 19

Author(s):

Anna C. Liang ◽

Emiri T. Mandeville ◽

Takakuni Maki ◽

Akihiro Shindo ◽

Angel T. Som ◽

...

Keyword(s):

Cerebral Ischemia ◽

Progenitor Cells ◽

Spontaneously Hypertensive Rats ◽

Focal Cerebral Ischemia ◽

Oligodendrocyte Precursor Cells ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Neural Stem Progenitor Cells ◽

Oligodendrocyte Precursor ◽

Effects Of Aging

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Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2

Scientific Reports ◽

10.1038/s41598-021-82931-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Linda L. Boshans ◽

Heun Soh ◽

William M. Wood ◽

Timothy M. Nolan ◽

Ion I. Mandoiu ◽

...

Keyword(s):

Transcription Factor ◽

Progenitor Cells ◽

Inhibitory Neuron ◽

Precursor Cells ◽

Synaptic Proteins ◽

Inhibitory Neurons ◽

Oligodendrocyte Precursor Cells ◽

Molecular Logic ◽

Neuronal Fate ◽

Oligodendrocyte Precursor

AbstractOligodendrocyte precursor cells (NG2 glia) are uniformly distributed proliferative cells in the mammalian central nervous system and generate myelinating oligodendrocytes throughout life. A subpopulation of OPCs in the neocortex arises from progenitor cells in the embryonic ganglionic eminences that also produce inhibitory neurons. The neuronal fate of some progenitor cells is sealed before birth as they become committed to the oligodendrocyte lineage, marked by sustained expression of the oligodendrocyte transcription factor Olig2, which represses the interneuron transcription factor Dlx2. Here we show that misexpression of Dlx2 alone in postnatal mouse OPCs caused them to switch their fate to GABAergic neurons within 2 days by downregulating Olig2 and upregulating a network of inhibitory neuron transcripts. After two weeks, some OPC-derived neurons generated trains of action potentials and formed clusters of GABAergic synaptic proteins. Our study revealed that the developmental molecular logic can be applied to promote neuronal reprogramming from OPCs.

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