photothrombotic-ischemia-minimally-invasive-reproducible

Photothrombotic Ischemia: A Minimally Invasive and Reproducible Photochemical Cortical Lesion Model for Mouse Stroke Studies

The photothrombotic stroke model aims to induce an ischemic damage within a given cortical area by means of photo-activation of a previously injected ...

University of Turin 

NG2-expressing cells comprise a population of cycling precursors that can exit the cell cycle and differentiate into mature oligodendrocytes. As a whole, they display heterogeneous properties and behaviors that remain unresolved at the molecular level, although partly interpretable as distinct maturation stages. To address this issue, we analyzed the expression of the GPR17 receptor, recently shown to decorate NG2-expressing cells and to operate as an early sensor of brain damage, in immature and adult oligodendrocyte progenitors in the intact brain and after injury. In both the early postnatal and adult cerebral cortex, distinct GPR17 protein localizations and expression levels define different stages of oligodendroglial maturation, ranging from the precursor phase to the premyelinating phenotype. As soon as cells exit mitosis, a fraction of NG2-expressing cells displays accumulation of GPR17 protein in the Golgi apparatus. GPR17 expression is subsequently upregulated and distributed to processes of cells that stop dividing, progressively lose NG2 positivity and assume premyelinating features. Absence of colabeling with mature markers or myelin proteins indicates that GPR17 is downregulated when cells complete their final maturation. BrdU-based fate-mapping demonstrated that a significant fraction of newly generated oligodendrocyte progenitors transiently upregulates GPR17 during maturation. Importantly, we also found that GPR17 does not participate to the early reaction of NG2-expressing cells to damage, while it is induced at postacute stages after injury. These findings identify GPR17 as a marker for progenitor progression within the oligodendroglial lineage and highlight its participation to postacute reactivity of NG2 cells in different injury paradigms.

The GPR17 receptor in NG2 expressing cells: focus on in vivo cell maturation and participation in acute trauma and chronic damage.

Les cellules exprimant le NG2 comportent une population de cyclisme pr&eacute;curseurs qui peuvent sortir du cycle cellulaire et se diff&eacute;rencier dans les oligodendrocytes matures. Ensemble, ils affichent propri&eacute;t&eacute;s h&eacute;t&eacute;rog&egrave;nes et les comportements qui restent en suspens au niveau mol&eacute;culaire, bien qu&#39;en partie interpr&eacute;tables comme stades de m&ucirc;rissement distinctes. Pour r&eacute;soudre ce probl&egrave;me, nous avons analys&eacute; l&#39;expression des r&eacute;cepteurs GPR17, r&eacute;cemment montr&eacute; pour d&eacute;corer des cellules exprimant le NG2 et de fonctionner comme un capteur pr&eacute;coce des l&eacute;sions c&eacute;r&eacute;brales, en prog&eacute;niteurs d&#39;oligodendrocytes immatures et d&#39;adultes dans le cerveau intact et apr&egrave;s une blessure. Dans le d&eacute;but postnatal et adult le cortex c&eacute;r&eacute;bral, distinctes localisations de prot&eacute;ines GPR17 et expression niveaux d&eacute;finissent diff&eacute;rents stades de maturation oligodendrogliale, allant de la phase de pr&eacute;curseur au ph&eacute;notype premyelinating. D&egrave;s que les cellules quitter mitose, une fraction des cellules exprimant le NG2 affiche l&#39;accumulation de prot&eacute;ine de GPR17 dans l&#39;appareil de Golgi. GPR17 expression est ensuite augment&eacute;e et distribu&eacute; aux processus des cellules qui arr&ecirc;tent le divisant, progressivement perdre NG2 positivit&eacute; et assumer les fonctions premyelinating. Absence de colabeling avec marqueurs matures ou des prot&eacute;ines de la my&eacute;line indique que GPR17 est diminu&eacute;e lorsque les cellules terminer leur maturation finale. Sort-cartographie BrdU ont d&eacute;montr&eacute; qu&#39;une fraction importante des cellules souches nouvellement g&eacute;n&eacute;r&eacute; oligodendrocyte transitoirement augmente GPR17 au cours de la maturation. Ce qui est important, nous avons &eacute;galement constat&eacute; que les GPR17 ne participe pas &agrave; la r&eacute;action rapide des cellules exprimant le NG2 aux dommages, tandis que l&#39;inspirent aux stades postacute apr&egrave;s une blessure. Ces constatations identifient GPR17 comme marqueur de la progression au sein de la lign&eacute;e oligodendrogliale prog&eacute;nitrices et soulignent sa participation &agrave; postacute r&eacute;activit&eacute; des cellules NG2 &agrave; des paradigmes de diff&eacute;rentes blessures.

Le r&eacute;cepteur GPR17 au NG2 exprimant des cellules : mettre l&#39;accent sur la maturation cellulaire in vivo et participation aux traumatismes aigus et chroniques.

Le cellule che esprimono NG2 comprendono una popolazione di ciclismo precursori che possono uscire il ciclo cellulare e differenziare in oligodendrociti maturi. Come un intero, visualizzano Propriet&agrave; eterogenee e comportamenti che restano irrisolti a livello molecolare, anche se in parte interpretabile come fasi distinte di maturazione. Per risolvere questo problema, abbiamo analizzato l&#39;espressione del recettore GPR17, recentemente mostrato per decorare le cellule che esprimono NG2 e funzionare come un sensore precoce di danni cerebrali, in progenitori immaturi e adulti oligodendrocyte nel cervello intatto e dopo l&#39;infortunio. In entrambi i primo postnatale e adulti corteccia cerebrale, distinte localizzazioni proteina GPR17 ed espressione livelli definiscono diversi stadi di maturazione oligodendrogliali, che vanno dalla fase di precursore per il fenotipo premyelinating. Non appena le cellule uscita mitosi, una frazione di cellule che esprimono NG2 Visualizza accumulo di proteina GPR17 nell&#39;apparato di Golgi. Espressione GPR17 &egrave; successivamente sovraregolati e distribuito ai processi delle cellule che smettere di dividendo, progressivamente perdono NG2 positivit&agrave; e assumere caratteristiche premyelinating. Assenza di colabeling con marcatori maturi o mielina proteine indica che GPR17 &egrave; downregolata quando cellule completano la loro maturazione finale. Destino-mapping basato su BrdU ha dimostrato che una frazione significativa dei progenitori oligodendrocyte appena generato transitoriamente sopraregola GPR17 le durante la maturazione. Soprattutto, abbiamo anche trovato che GPR17 non partecipa alla reazione precoce delle cellule NG2-esprimere ai danni, mentre &egrave; indotta a stadi postacute dopo l&#39;infortunio. Questi risultati identificano GPR17 come un marcatore di progressione progenitore all&#39;interno del lignaggio oligodendrogliali ed evidenziano la sua partecipazione a postacute reattivit&agrave; delle cellule NG2 paradigmi differenti lesioni.

Vivien Labat-gest

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