Spinal cord injury induces astroglial conversion towards neuronal lineageReport as inadecuate




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Molecular Neurodegeneration

, 11:68

First Online: 06 October 2016Received: 11 March 2016Accepted: 28 September 2016

Abstract

BackgroundNeurons have intrinsic capability to regenerate after lesion, though not spontaneously. Spinal cord injury SCI causes permanent neurological impairments partly due to formation of a glial scar that is composed of astrocytes and microglia. Astrocytes play both beneficial and detrimental roles on axonal re-growth, however, their precise role after SCI is currently under debate.

MethodsWe analyzed molecular changes in astrocytes at multiple stages after two SCI severities using cell-specific transcriptomic analyses.

ResultsWe demonstrate that astrocyte response after injury depends on both time after injury and lesion severity. We then establish that injury induces an autologous astroglial transdifferentiation where over 10 % of astrocytes express classical neuronal progenitor markers including βIII-tubulin and doublecortin with typical immature neuronal morphology. Lineage tracing confirmed that the origin of these astrocytes is resident mature, rather than newly formed astrocytes. Astrocyte-derived neuronal progenitors subsequently express GABAergic, but not glutamatergic-specific markers. Furthermore, we have identified the neural stem cell marker fibroblast growth factor receptor 4 Fgfr4 as a potential autologous modulator of astrocytic transdifferentiation following SCI. Finally, we establish that astroglial transdifferentiation into neuronal progenitors starts as early as 72 h and continues to a lower degrees up to 6 weeks post-lesion.

ConclusionWe thus demonstrate for the first time autologous injury-induced astroglial conversion towards neuronal lineage that may represent a therapeutic strategy to replace neuronal loss and improve functional outcomes after central nervous system injury.

KeywordsSpinal cord injury Astrocytes Astrogliosis Transdifferentiation Cell specific transcriptomic Abbreviations7-AAD7-aminoactinomycin

Aldh1L1Aldehyde dehydrogenase 1 family member L1

DCXDoublecortin

eGFPEnhanced green fluorescent protein

FACSFluorescence-activated cell sorting

Fgfr4Fibroblast growth factor receptor 4

FTFull transection

GAD 65-67Glutamate decarboxylase

HSHemisection

MMRRCMutant Mouse Regional Resource Centre

NeuNNeuronal nucleus

NINon-injured

PBSPhosphate base saline

PFAParaformaldehyde

RNA-SeqRNA sequencing

SCISpinal cord injury

Tlx3-RnxT-cell leukemia homeo box 3

Electronic supplementary materialThe online version of this article doi:10.1186-s13024-016-0133-0 contains supplementary material, which is available to authorized users.

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Author: Harun Najib Noristani - Jean Charles Sabourin - Hassan Boukhaddaoui - Emilie Chan-Seng - Yannick Nicolas Gerber - Florence

Source: https://link.springer.com/article/10.1186/s13024-016-0133-0



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