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利用ROS的动态变化表征海马神经干细胞功能状态的转换
2020-12-04 13:45

德国神经退行性疾病研究中心(DZNE) Gerd Kempermann课题组在研究中取得进展。他们研究发现活性氧(ROS)的动态变化可表征海马神经干细胞的功能状态,并与其从活动依赖性静息状态退出相关。该研究于2020年12月3日在线发表于国际学术期刊《细胞-干细胞》。

与细胞内ROS含量的一般规律相反,研究人员发现在成年小鼠海马体中,静止态神经前体细胞(NPC)保持最高水平的ROS(hiROS)。依据细胞内ROS的含量对NPC进行分类可确定不同的功能状态。ROS含量的变化诱导了细胞后续状态的转换,其中较低水平的ROS标志着增殖活性和分化。体力活动是成人海马神经发生的生理激活剂,它通过瞬时Nox2依赖的ROS激增招募hiROS NPCs并使其增殖。在没有Nox2的情况下,基线神经发生不受影响,但激活诱导的增殖增加却消失了。

这些结果提供了NPC功能状态的代谢分类,并揭示了通过行为活动将细胞内ROS的调控与成人NPC激活联系起来的机制。

据悉,细胞氧化还原状态调节干细胞静息与激活之间的平衡。细胞内ROS水平的提高与增殖和谱系特异性有关。

附:英文原文

Title: ROS Dynamics Delineate Functional States of Hippocampal Neural Stem Cells and Link to Their Activity-Dependent Exit from Quiescence

Author: Vijay S. Adusumilli, Tara L. Walker, Rupert W. Overall, Gesa M. Klatt, Salma A. Zeidan, Sara Zocher, Dilyana G. Kirova, Konstantinos Ntitsias, Tim J. Fischer, Alex M. Sykes, Susanne Reinhardt, Andreas Dahl, Jrg Mansfeld, Annette E. Rünker, Gerd Kempermann

Issue&Volume: 2020-12-03

Abstract: Cellular redox states regulate the balance between stem cell maintenance and activation. Increased levels of intracellular reactive oxygen species (ROS) are linked to proliferation and lineage specification. In contrast to this general principle, we here show that in the hippocampus of adult mice, quiescent neural precursor cells (NPCs) maintain the highest ROS levels (hiROS). Classifying NPCs on the basis of cellular ROS content identified distinct functional states. Shifts in ROS content primed cells for a subsequent state transition, with lower ROS content marking proliferative activity and differentiation. Physical activity, a physiological activator of adult hippocampal neurogenesis, recruited hiROS NPCs into proliferation via a transient Nox2-dependent ROS surge. In the absence of Nox2, baseline neurogenesis was unaffected, but the activity-induced increase in proliferation disappeared. These results provide a metabolic classification of NPC functional states and describe a mechanism linking the modulation of cellular ROS by behavioral cues to the activation of adult NPCs.

DOI: 10.1016/j.stem.2020.10.019

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30538-5

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:25.269
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx


本期文章:《细胞—干细胞》:Online/在线发表

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