Multimodal charting of molecular and functional cell states via in situ electro-sequencing-猫眼课题宝

DOI：

10.1016/j.cell.2023.03.023

发表时间：

2023-04

期刊：

Cell

影响因子：

64.5

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Qiang Li;Zuwan Lin;Ren Liu;Xin-Hui Tang;Jiahao Huang;Yichun He;Xin Sui;Weiwen Tian;Haolan Shen;Haowen Zhou;Hao Sheng;Hailing Shi;Li Xiao;Xiao Wang;Jia Liu

单细胞基因表达和电生理学的配对绘图对于了解生电组织中基因与功能的关系至关重要。在这里，我们开发了原位电测序（electro-seq），它结合了situRNA测序中的灵活生物电子学，以稳定地映射毫秒时间尺度的电活动，并分析来自完整生物网络（包括心脏和神经补丁）的相同细胞的单细胞基因表达。当应用于人类诱导的多能干细胞衍生的心肌细胞贴片时，原位电测序能够在细胞水平上对心肌细胞电生理和基因表达进行多模态原位分析，共同定义细胞状态和发育轨迹。使用基于机器学习的交叉模态分析，原位电测序识别了心肌细胞发育过程中基因与电生理的关系，并基于长期稳定的电测量准确重建了基因表达谱的演变。原位电测序可用于创建生电组织中的时空多模态图谱，加强了对负责电生理功能和功能障碍的细胞类型和基因程序的发现。

Paired mapping of single-cell gene expression and electrophysiology is essential to understand gene-to-function relationships in electrogenic tissues. Here, we developedin situelectro-sequencing (electro-seq) that combines flexible bioelectronics within situRNA sequencing to stably map millisecond-timescale electrical activity and profile single-cell gene expression from the same cells across intact biological networks, including cardiac and neural patches. When applied to human-induced pluripotent stem-cell-derived cardiomyocyte patches,in situelectro-seq enabled multimodalin situanalysis of cardiomyocyte electrophysiology and gene expression at the cellular level, jointly defining cell states and developmental trajectories. Using machine-learning-based cross-modal analysis,in situelectro-seq identified gene-to-electrophysiology relationships throughout cardiomyocyte development and accurately reconstructed the evolution of gene expression profiles based on long-term stable electrical measurements.In situelectro-seq could be applicable to create spatiotemporal multimodal maps in electrogenic tissues, potentiating the discovery of cell types and gene programs responsible for electrophysiological function and dysfunction.

Multimodal charting of molecular and functional cell states via in situ electro-sequencing

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