瑞士联邦理工学院Grégoire Courtine等研究人员合作绘制出Tabulae Paralytica中的脊髓损伤单细胞和空间图谱。该项研究成果于2024年6月19日在线发表在《自然》杂志上。

研究人员介绍了Tabulae Paralytica——脊髓损伤（SCI）的四个图谱汇编，包括一个50万个细胞的单核转录组图谱、一个将同一细胞核内的转录组和表观基因组测量配对的多组图谱，以及两个跨越四个空间和时间维度的损伤脊髓空间转录组图谱。研究人员将这些图谱整合到一个共同的框架中，以剖析支配脊髓内损伤反应的分子逻辑。

Tabulae Paralytica揭示了决定脊髓损伤后果的新生物学原理，包括神经元对损伤反应的保守性和差异性；损伤后特定神经元亚群上调回路重组程序的先导性；神经元应激反应与回路重组程序激活之间的反比关系；脊髓损伤后在免疫优势环境和神经外环境之间重建三方神经保护屏障的必要性，以及老龄小鼠未能形成这一屏障。

研究人员利用Tabulae Paralytica开发了一种恢复活力的基因疗法，重建了这三方屏障，恢复了老龄小鼠瘫痪后行走的自然恢复能力。Tabulae Paralytica为了解SCI的病理生物学提供了一个窗口，同时为在四个维度上整合多模态、基因组尺度的测量建立了一个框架，以研究生物学和医学。

附：英文原文

Title: Single-cell and spatial atlases of spinal cord injury in the Tabulae Paralytica

Author: Skinnider, Michael A., Gautier, Matthieu, Teo, Alan Yue Yang, Kathe, Claudia, Hutson, Thomas H., Laskaratos, Achilleas, de Coucy, Alexandra, Regazzi, Nicola, Aureli, Viviana, James, Nicholas D., Schneider, Bernard, Sofroniew, Michael V., Barraud, Quentin, Bloch, Jocelyne, Anderson, Mark A., Squair, Jordan W., Courtine, Grgoire

Issue&Volume: 2024-06-19

Abstract: Here, we introduce the Tabulae Paralytica—a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells, a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei, and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord1. The Tabulae Paralytica uncovered new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to upregulate circuit-reorganizing programs after injury; an inverse relationship between neuronal stress responses and the activation of circuit reorganization programs; the necessity of re-establishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI and a failure to form this barrier in old mice. We leveraged the Tabulae Paralytica to develop a rejuvenative gene therapy that re-established this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The Tabulae Paralytica provides a window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.

DOI: 10.1038/s41586-024-07504-y

Source: https://www.nature.com/articles/s41586-024-07504-y