1 Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan.
2 Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.
Stem Cells Dev. 2019 Apr 15;28(8):528-542. doi: 10.1089/scd.2018.0232. Epub 2019 Mar 18.
There is compelling evidence that the mature central nervous system (CNS) harbors stem cell populations outside conventional neurogenic regions. We previously demonstrated that brain pericytes (PCs) in both mouse and human exhibit multipotency to differentiate into various neural lineages following cerebral ischemia. PCs are found throughout the CNS, including cerebellum, but it remains unclear whether cerebellar PCs also form ischemia-induced multipotent stem cells (iSCs). In this study, we demonstrate that putative iSCs can be isolated from poststroke human cerebellum (cerebellar iSCs [cl-iSCs]). These cl-iSCs exhibited multipotency and differentiated into electrophysiologically active neurons. Neurogenic potential was also confirmed in single-cell suspensions. DNA microarray analysis revealed highly similar gene expression patterns between PCs and cl-iSCs, suggesting PC origin. Global gene expression comparison with cerebral iSCs revealed general similarity, but cl-iSCs differentially expressed certain cerebellum-specific genes. Thus, putative iSCs are present in poststroke cerebellum and possess region-specific traits, suggesting potential capacity to regenerate functional cerebellar neurons following ischemic stroke.
有确凿的证据表明,成熟的中枢神经系统(CNS)在传统的神经发生区域之外存在干细胞群体。我们之前的研究表明,无论是在小鼠还是人类中,脑周细胞(PC)在脑缺血后都具有多能性,可以分化为各种神经谱系。PC 存在于整个中枢神经系统,包括小脑,但目前尚不清楚小脑 PC 是否也形成缺血诱导的多能干细胞(iSCs)。在这项研究中,我们证明了脑卒中后人类小脑(小脑 iSCs [cl-iSCs])中可以分离出假定的 iSCs。这些 cl-iSCs 表现出多能性,并分化为电生理活性神经元。单细胞悬液中也证实了神经发生潜能。DNA 微阵列分析显示 PC 和 cl-iSCs 之间的基因表达模式高度相似,提示 PC 的起源。与脑 iSCs 的全基因组表达比较显示出一般的相似性,但 cl-iSCs 差异表达某些小脑特异性基因。因此,脑卒中后的小脑中存在假定的 iSCs,具有区域特异性特征,提示其在缺血性脑卒中后具有再生功能性小脑神经元的潜力。