Ge Xiaoqian, Xu Xueqi, Cai Qi, Xiong Hejian, Chen Xie, Hong Yi, Gao Xiaofei, Yao Yao, Bachoo Robert, Qin Zhenpeng
bioRxiv. 2023 Mar 31:2023.03.29.534827. doi: 10.1101/2023.03.29.534827.
The brain extracellular matrix (ECM), consisting of proteins and glycosaminoglycans, is a critical scaffold in the development, homeostasis, and disorders of the central nervous system (CNS) and undergoes remodeling in response to environmental cues. Live imaging of brain ECM structure represents a native view of the brain ECM but, until now, remains challenging due to the lack of a robust fluorescent labeling approach. Here, we developed a pan-ECM method for labeling the entire (Greek: pan) brain ECM network by screening and delivering a protein-reactive dye into the brain. pan-ECM enables imaging of ECM compartments in live brain tissue, including the interstitial matrix, basement membrane (BM), and perineuronal nets (PNNs), and even the ECM in glioblastoma and stroke mouse brains. This approach provides access to the structure and dynamics of the ECM and enhances our understanding of the complexities of the brain ECM and its contribution to brain health and disease.
脑细胞外基质(ECM)由蛋白质和糖胺聚糖组成,是中枢神经系统(CNS)发育、稳态及疾病过程中的关键支架,并会根据环境信号进行重塑。脑ECM结构的实时成像代表了脑ECM的自然状态,但迄今为止,由于缺乏强大的荧光标记方法,这一过程仍具有挑战性。在此,我们开发了一种全脑ECM方法,通过筛选并向脑内递送一种蛋白质反应性染料来标记整个(希腊语:pan)脑ECM网络。全脑ECM方法能够对活脑组织中的ECM区室进行成像,包括细胞间质、基底膜(BM)和神经元周围网(PNN),甚至还能对胶质母细胞瘤和中风小鼠脑内的ECM进行成像。这种方法为研究ECM的结构和动态变化提供了途径,增进了我们对脑ECM复杂性及其对脑健康和疾病影响的理解。