Malik Astha, Jamasbi Roudabeh J, Kondratov Roman V, Geusz Michael E
Department of Biology, Bowling Green State University, Bowling Green, Ohio, United States of America.
Department of Biology, Bowling Green State University, Bowling Green, Ohio, United States of America; Department of Public and Allied Health, Bowling Green State University, Bowling Green, Ohio, United States of America.
PLoS One. 2015 Mar 31;10(3):e0122937. doi: 10.1371/journal.pone.0122937. eCollection 2015.
Circadian rhythms are common in many cell types but are reported to be lacking in embryonic stem cells. Recent studies have described possible interactions between the molecular mechanism of circadian clocks and the signaling pathways that regulate stem cell differentiation. Circadian rhythms have not been examined well in neural stem cells and progenitor cells that produce new neurons and glial cells during adult neurogenesis. To evaluate circadian timing abilities of cells undergoing neural differentiation, neurospheres were prepared from the mouse subventricular zone (SVZ), a rich source of adult neural stem cells. Circadian rhythms in mPer1 gene expression were recorded in individual spheres, and cell types were characterized by confocal immunofluorescence microscopy at early and late developmental stages in vitro. Circadian rhythms were observed in neurospheres induced to differentiate into neurons or glia, and rhythms emerged within 3-4 days as differentiation proceeded, suggesting that the neural stem cell state suppresses the functioning of the circadian clock. Evidence was also provided that neural stem progenitor cells derived from the SVZ of adult mice are self-sufficient clock cells capable of producing a circadian rhythm without input from known circadian pacemakers of the organism. Expression of mPer1 occurred in high frequency oscillations before circadian rhythms were detected, which may represent a role for this circadian clock gene in the fast cycling of gene expression responsible for early cell differentiation.
昼夜节律在许多细胞类型中普遍存在，但据报道胚胎干细胞中缺乏昼夜节律。最近的研究描述了生物钟的分子机制与调节干细胞分化的信号通路之间可能存在的相互作用。在成年神经发生过程中产生新的神经元和神经胶质细胞的神经干细胞和祖细胞中，昼夜节律尚未得到充分研究。为了评估神经分化细胞的昼夜计时能力，从小鼠脑室下区（SVZ）制备了神经球，该区域是成年神经干细胞的丰富来源。在单个神经球中记录mPer1基因表达的昼夜节律，并通过共聚焦免疫荧光显微镜在体外发育的早期和晚期对细胞类型进行表征。在诱导分化为神经元或神经胶质细胞的神经球中观察到昼夜节律，并且随着分化的进行，节律在3-4天内出现，这表明神经干细胞状态抑制了生物钟的功能。还提供了证据表明，源自成年小鼠SVZ的神经干细胞祖细胞是能够产生昼夜节律的自给自足的生物钟细胞，无需生物体已知的昼夜起搏器的输入。在检测到昼夜节律之前，mPer1的表达以高频振荡出现，这可能代表该生物钟基因在负责早期细胞分化的基因快速循环中的作用。
