美国斯坦福大学Alice Y. Ting和Karl Deisseroth研究团队合作取得最新进展。他们利用分子钙整合子技术揭示了纹状体细胞类型的驱动厌恶。2020年12月11日出版的《细胞》杂志发表了这项成果。

他们报告了一种分子技术，用于细胞的稳定遗传标记，这些细胞在细胞内钙浓度（FLiCRE）中表现出与活动相关的增加。在短暂刺激厌恶性输入的过程中，他们使用FLiCRE转录标记了小鼠大脑伏隔核中的活跃神经群。使用单细胞RNA测序，他们检测到内源性转录组中的FLiCRE转录本，同时提供了细胞类型和钙激活史读数。

他们在远距离兴奋性映射的下游激活伏隔核中确定了一种细胞类型。利用FLiCRE的模块化设计，他们选择性地在这种细胞类型中表达了一条光遗传学通道，并表明是直接募集，这种原本无法通过遗传学获得的群体会引起行为反感。 FLiCRE的特异性和微小的分辨率使分子传递出表征、操纵和重新编程的活化细胞团信息。

据介绍，记录细胞DNA或RNA中瞬时细胞事件的能力将使精确、大规模的分析、选择和重新编程异质细胞群体成为可能。

附：英文原文

Title: A Molecular Calcium Integrator Reveals a Striatal Cell Type Driving Aversion

Author: Christina K. Kim, Mateo I. Sanchez, Paul Hoerbelt, Lief E. Fenno, Robert C. Malenka, Karl Deisseroth, Alice Y. Ting

Issue&Volume: 2020-12-11

Abstract: The ability to record transient cellular events in the DNA or RNA of cells would enableprecise, large-scale analysis, selection, and reprogramming of heterogeneous cellpopulations. Here, we report a molecular technology for stable genetic tagging ofcells that exhibit activity-related increases in intracellular calcium concentration(FLiCRE). We used FLiCRE to transcriptionally label activated neural ensembles inthe nucleus accumbens of the mouse brain during brief stimulation of aversive inputs.Using single-cell RNA sequencing, we detected FLiCRE transcripts among the endogenoustranscriptome, providing simultaneous readout of both cell-type and calcium activationhistory. We identified a cell type in the nucleus accumbens activated downstream oflong-range excitatory projections. Taking advantage of FLiCRE’s modular design, weexpressed an optogenetic channel selectively in this cell type and showed that directrecruitment of this otherwise genetically inaccessible population elicits behavioralaversion. The specificity and minute resolution of FLiCRE enables molecularly informedcharacterization, manipulation, and reprogramming of activated cellular ensembles.

DOI: 10.1016/j.cell.2020.11.015

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31532-4