Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination.
Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination.
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作者：
Baxi EG;DeBruin J;Jin J;Strasburger HJ;Smith MD;Orthmann-Murphy JL;Schott JT;Fairchild AN;Bergles DE;Calabresi PA
少突胶质细胞的再生是从脱髓鞘中恢复的关键步骤，因为存活的少突胶质细胞结构可塑性有限，很少形成额外的髓鞘。新的少突胶质细胞是通过表达广泛分布于中枢神经系统的少突胶质前体细胞(OPC)的血小板衍生生长因子受体α(PDGFRα)分化而来的。尽管已经对这些前体细胞在白质中的行为进行了详细的调查，但最近的研究表明，多发性硬化症(MS)的疾病负担与灰质萎缩更密切相关。灰质重新髓鞘形成的时间和效率与白质不同，但导致这些差异的OPC的动态还没有确定。在这里，我们使用体内遗传命运追踪来确定灰质和白质区域OPC在铜酮诱导的脱髓鞘反应中的行为。我们的研究表明，OPC分化的时间动力学在白质和灰质之间存在显著差异。当OPC迅速地重新填充到胼胝体并成熟为表达成熟少突胶质细胞的CC1时，扣带皮质和海马区的OPC分化速度要慢得多，导致重新髓鞘形成的时间相对于胼胝体延迟。灰质中OPC的长期成熟可能是MS更大的轴突病理和疾病负担的原因。
The regeneration of oligodendrocytes is a crucial step in recovery from demyelination, as surviving oligodendrocytes exhibit limited structural plasticity and rarely form additional myelin sheaths. New oligodendrocytes arise through the differentiation of platelet-derived growth factor receptor α (PDGFRα) expressing oligodendrocyte progenitor cells (OPCs) that are widely distributed throughout the CNS. Although there has been detailed investigation of the behavior of these progenitors in white matter, recent studies suggest that disease burden in multiple sclerosis (MS) is more strongly correlated with gray matter atrophy. The timing and efficiency of remyelination in gray matter is distinct from white matter, but the dynamics of OPCs that contribute to these differences have not been defined. Here we used in vivo genetic fate tracing to determine the behavior of OPCs in gray and white matter regions in response to cuprizone-induced demyelination. Our studies indicate that the temporal dynamics of OPC differentiation varies significantly between white and gray matter. While OPCs rapidly repopulate the corpus callosum and mature into CC1 expressing mature oligodendrocytes, OPC differentiation in the cingulate cortex and hippocampus occurs much more slowly, resulting in a delay in remyelination relative to the corpus callosum. The protracted maturation of OPCs in gray matter may contribute to greater axonal pathology and disease burden in MS.
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影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
影响因子：
11.2
作者：
Chang, Ansi;Staugaitis, Susan M.;Dutta, Ranjan;Batt, Courtney E.;Easley, Kathryn E.;Chomyk, Anthony M.;Yong, V. Wee;Fox, Robert J.;Kidd, Grahame J.;Trapp, Bruce D.
通讯作者：
Trapp, Bruce D.
影响因子：
6.4
作者：
Albert, Monika;Antel, Jack;Stadelmann, Christine
通讯作者：
Stadelmann, Christine
影响因子：
64.8
作者：
Fuenfschilling, Ursula;Supplie, Lotti M.;Mahad, Don;Boretius, Susann;Saab, Aiman S.;Edgar, Julia;Brinkmann, Bastian G.;Kassmann, Celia M.;Tzvetanova, Iva D.;Moebius, Wiebke;Diaz, Francisca;Meijer, Dies;Suter, Ueli;Hamprecht, Bernd;Sereda, Michael W.;Moraes, Carlos T.;Frahm, Jens;Goebbels, Sandra;Nave, Klaus-Armin
通讯作者：
Nave, Klaus-Armin
影响因子：
4.7
作者：
Hibbits N;Yoshino J;Le TQ;Armstrong RC
通讯作者：
Armstrong RC