Department of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Department of Neurology, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cells. 2022 Feb 18;11(4):721. doi: 10.3390/cells11040721.
There is growing appreciation for astrocyte heterogeneity both across and within central nervous system (CNS) regions, as well as between intact and diseased states. Recent work identified multiple astrocyte subpopulations in mature brain. Interestingly, one subpopulation (Population C) was shown to possess significantly enhanced synaptogenic properties in vitro, as compared with other astrocyte subpopulations of adult cortex and spinal cord. Following spinal cord injury (SCI), damaged neurons lose synaptic connections with neuronal partners, resulting in persistent functional loss. We determined whether SCI induces an enhanced synaptomodulatory astrocyte phenotype by shifting toward a greater proportion of Population C cells and/or increasing expression of relevant synapse formation-associated genes within one or more astrocyte subpopulations. Using flow cytometry and RNAscope in situ hybridization, we found that astrocyte subpopulation distribution in the spinal cord did not change to a selectively synaptogenic phenotype following mouse cervical hemisection-type SCI. We also found that spinal cord astrocytes expressed synapse formation-associated genes to a similar degree across subpopulations, as well as in an unchanged manner between uninjured and SCI conditions. Finally, we confirmed these astrocyte subpopulations are also present in the human spinal cord in a similar distribution as mouse, suggesting possible conservation of spinal cord astrocyte heterogeneity across species.
人们越来越意识到，中枢神经系统（CNS）区域之间以及正常状态和疾病状态之间的星形胶质细胞存在异质性。最近的研究在成熟大脑中鉴定出多个星形胶质细胞亚群。有趣的是，与成年大脑皮层和脊髓中的其他星形胶质细胞亚群相比，其中一个亚群（C 群）在体外具有明显增强的突触发生特性。脊髓损伤（SCI）后，受损神经元失去与神经元伙伴的突触连接，导致持续的功能丧失。我们确定 SCI 是否通过增加 C 群细胞的比例和/或增加一个或多个星形胶质细胞亚群中与相关突触形成相关的基因表达来诱导增强的突触调节星形胶质细胞表型。通过流式细胞术和 RNAscope 原位杂交，我们发现，在小鼠颈半切型 SCI 后，脊髓中星形胶质细胞亚群的分布并没有向选择性突触发生表型转变。我们还发现，脊髓星形胶质细胞在亚群之间以及在未受伤和 SCI 条件下以相似的程度表达与突触形成相关的基因。最后，我们证实这些星形胶质细胞亚群在人类脊髓中也以类似于小鼠的方式存在，这表明不同物种的脊髓星形胶质细胞异质性可能具有保守性。
