美国威斯康星大学Darcie L. Moore课题组发现，自发荧光是神经干细胞活化状态的生物标记。2024年3月22日，国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

研究人员表示，神经干细胞（NSC）必须退出静止期才能产生神经元；然而，人们对这一过程的了解仍然受到现有技术的限制。自发荧光代谢辅因子的荧光寿命成像（FLIM）已被用于其他细胞类型，以研究细胞状态在代谢重塑驱动下的转变，代谢重塑改变了这些内源性荧光团的光学特性。

利用这种非破坏性、活细胞和无标记的策略，研究人员发现静止的NSC（qNSC）和活化的NSC（aNSC）具有独特的自发荧光特征。具体来说，qNSC的自发荧光富集于溶酶体亚群，可作为NSC静止的分级标记，并以单细胞分辨率来预测细胞行为。将自发荧光成像与单细胞RNA测序结合起来，研究人员提供了揭示与深度静止和快速NSC激活相关的转录特征的资源。总之，研究人员描述了一种跟踪小鼠NSC激活状态的方法，并拓展了人们对成体神经发生的理解。

附：英文原文

Title: Autofluorescence is a biomarker of neural stem cell activation state

Author: Christopher S. Morrow, Kelsey Tweed, Sabina Farhadova, Alex J. Walsh, Bo P. Lear, Avtar Roopra, Ryan D. Risgaard, Payton C. Klosa, Zachary P. Arndt, Ella R. Peterson, Michelle M. Chi, Allison G. Harris, Melissa C. Skala, Darcie L. Moore

Issue&Volume: 2024-03-22

Abstract: Neural stem cells (NSCs) must exit quiescence to produce neurons; however, our understandingof this process remains constrained by the technical limitations of current technologies.Fluorescence lifetime imaging (FLIM) of autofluorescent metabolic cofactors has beenused in other cell types to study shifts in cell states driven by metabolic remodelingthat change the optical properties of these endogenous fluorophores. Using this non-destructive,live-cell, and label-free strategy, we found that quiescent NSCs (qNSCs) and activatedNSCs (aNSCs) have unique autofluorescence profiles. Specifically, qNSCs display anenrichment of autofluorescence localizing to a subset of lysosomes, which can be usedas a graded marker of NSC quiescence to predict cell behavior at single-cell resolution.Coupling autofluorescence imaging with single-cell RNA sequencing, we provide resourcesrevealing transcriptional features linked to deep quiescence and rapid NSC activation.Together, we describe an approach for tracking mouse NSC activation state and expandour understanding of adult neurogenesis.

DOI: 10.1016/j.stem.2024.02.011

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00054-7