Live imaging of remyelination in the adult mouse corpus callosum.
Live imaging of remyelination in the adult mouse corpus callosum.
复制标题
DOI：
10.1073/pnas.2025795118
复制
发表时间：
2021-07-13
影响因子：
11.1
通讯作者：
Jessberger S
中科院分区：
文献类型：
--
作者：
Bottes S;Jessberger S
少突胶质细胞前体细胞（OPCs）在脱髓鞘损伤后保持轴突髓鞘再生的能力。然而，在脑深部结构，如胼胝体中的单个OPCs的细胞分裂和分化动力学模式仍然未知。使用体内双光子成像在一个局灶模型脱髓鞘，我们表明，OPCs经历了几轮对称和不对称的细胞分裂，然后产生一个子集的子细胞分化成髓鞘少突胶质细胞。这里呈现的数据表征OPC克隆的行为，并描绘了导致髓鞘再生的细胞原则。少突胶质细胞前体细胞（OPCs）在脱髓鞘后保留了胼胝体（CC）中轴突髓鞘再生的能力。然而，由于缺乏对受损脑内单个细胞的纵向观察，OPC激活的动力学、细胞分裂、迁移和分化模式在单细胞水平上仍然知之甚少。在成年小鼠CC中用溶血磷脂酰胆碱诱导局灶性脱髓鞘后，我们使用双光子显微镜观察了长达2个月的OPCs及其分化后代，通过基因Achaete-scute同源物1的调控元件驱动的条件重组进行遗传标记。OPCs经历了几轮对称和不对称的细胞分裂，产生了一个亚群的子细胞分化成髓鞘少突胶质细胞。虽然OPC继续增殖，但分化成髓鞘少突胶质细胞的能力随着时间的推移而下降，OPC衍生的子细胞的死亡增加。因此，慢性体内成像描绘了导致成人脑髓鞘再生的细胞原理，为开发增强急性和慢性脱髓鞘疾病内源性脑修复的策略提供了框架。
Oligodendrocyte precursor cells (OPCs) retain the capacity to remyelinate axons upon demyelinating injury. However, mode of cell division and differentiation dynamics of individual OPCs in deep brain structures, such as the corpus callosum, remains unknown. Using in vivo two-photon imaging in a focal model of demyelination, we show that OPCs undergo several rounds of symmetric and asymmetric cell divisions before producing a subset of daughter cells that differentiates into myelinating oligodendrocytes. The data presented here characterize the behavior of OPC clones and delineate the cellular principles that lead to remyelination. Oligodendrocyte precursor cells (OPCs) retain the capacity to remyelinate axons in the corpus callosum (CC) upon demyelination. However, the dynamics of OPC activation, mode of cell division, migration, and differentiation on a single-cell level remain poorly understood due to the lack of longitudinal observations of individual cells within the injured brain. After inducing focal demyelination with lysophosphatidylcholin in the CC of adult mice, we used two-photon microscopy to follow for up to 2 mo OPCs and their differentiating progeny, genetically labeled through conditional recombination driven by the regulatory elements of the gene Achaete-scute homolog 1. OPCs underwent several rounds of symmetric and asymmetric cell divisions, producing a subset of daughter cells that differentiates into myelinating oligodendrocytes. While OPCs continue to proliferate, differentiation into myelinating oligodendrocytes declines with time, and death of OPC-derived daughter cells increases. Thus, chronic in vivo imaging delineates the cellular principles leading to remyelination in the adult brain, providing a framework for the development of strategies to enhance endogenous brain repair in acute and chronic demyelinating disease.
登录
查看更多内容
DOI：
10.1523/jneurosci.0805-13.2013
发表时间：
2013-06-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Nakatani H;Martin E;Hassani H;Clavairoly A;Maire CL;Viadieu A;Kerninon C;Delmasure A;Frah M;Weber M;Nakafuku M;Zalc B;Thomas JL;Guillemot F;Nait-Oumesmar B;Parras C
通讯作者：
Parras C
影响因子：
25
作者：
Hughes EG;Orthmann-Murphy JL;Langseth AJ;Bergles DE
通讯作者：
Bergles DE
影响因子：
6.2
作者：
Baxi EG;DeBruin J;Jin J;Strasburger HJ;Smith MD;Orthmann-Murphy JL;Schott JT;Fairchild AN;Bergles DE;Calabresi PA
通讯作者：
Calabresi PA
影响因子：
14.5
作者：
Hunter, SF;Leavitt, JA;Rodriguez, M
通讯作者：
Rodriguez, M
影响因子：
5.7
作者：
Ma J;Shen Z;Yu YC;Shi SH
通讯作者：
Shi SH