Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, P. R. China.
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, P. R. China.
Sci Adv. 2023 Oct 20;9(42):eadi1891. doi: 10.1126/sciadv.adi1891. Epub 2023 Oct 18.
Skeletal muscle regeneration requires the highly coordinated cooperation of muscle satellite cells (MuSCs) with other cellular components. Upon injury, myeloid cells populate the wound site, concomitant with MuSC activation. However, detailed analysis of MuSC-myeloid cell interaction is hindered by the lack of suitable live animal imaging technology. Here, we developed a dual-laser multimodal nonlinear optical microscope platform to study the dynamics of MuSCs and their interaction with nonmyogenic cells during muscle regeneration. Using three-dimensional time-lapse imaging on live reporter mice and taking advantages of the autofluorescence of reduced nicotinamide adenine dinucleotide (NADH), we studied the spatiotemporal interaction between nonmyogenic cells and muscle stem/progenitor cells during MuSC activation and proliferation. We discovered that their cell-cell contact was transient in nature. Moreover, MuSCs could activate with notably reduced infiltration of neutrophils and macrophages, and their proliferation, although dependent on macrophages, did not require constant contact with them. These findings provide a fresh perspective on myeloid cells' role during muscle regeneration.
骨骼肌再生需要肌肉卫星细胞（MuSCs）与其他细胞成分高度协调合作。在损伤时，髓系细胞会在 MuSC 激活的同时浸润到损伤部位。然而，MuSC 与髓系细胞相互作用的详细分析受到缺乏合适的活体动物成像技术的限制。在这里，我们开发了一种双激光多模态非线性光学显微镜平台，用于研究肌肉再生过程中 MuSCs 的动力学及其与非肌细胞的相互作用。我们利用活报告小鼠的三维延时成像，并利用还原型烟酰胺腺嘌呤二核苷酸（NADH）的自发荧光，研究了 MuSC 激活和增殖过程中非肌细胞与肌肉干细胞/祖细胞之间的时空相互作用。我们发现它们的细胞-细胞接触是短暂的。此外，MuSCs 的激活过程中浸润的中性粒细胞和巨噬细胞明显减少，而它们的增殖虽然依赖于巨噬细胞，但并不需要与它们持续接触。这些发现为髓系细胞在肌肉再生过程中的作用提供了新的视角。
