Abstract：
Cellular heterogeneity is a well-accepted feature of tissues, and both transcriptional and metabolic diversity have been revealed by numerous approaches, including optical imaging. However, the high magnification objective lenses needed for high-resolution imaging provides information from only small layers of tissue, which can result in poor cell statistics. There is therefore an unmet need for an imaging modality that can provide detailed molecular and cellular insight within intact tissue samples in 3D. Using GFP-tagged GLUT4 as proof of concept, we present here a novel optical mesoscopy approach that allows precise measurement of the spatial location of GLUT4 within specific anatomical structures across the myocardium in ultrathick sections (5 mm x 5 mm x 3 mm) of intact mouse heart. We reveal distinct GLUT4 distribution patterns across cardiac walls and highlight specific changes in GLUT4 expression levels in response to high fat diet-feeding, and we identify sex-dependent differences in expression patterns. This method is applicable to any target that can be labelled for light microscopy, and to other complex tissues when organ structure needs to be considered simultaneously with cellular detail.
摘要：
细胞异质性是一个公认的组织特征，转录和代谢多样性已经被许多方法揭示，包括光学成像。然而,高分辨率成像所需的高倍率物镜仅提供来自小层组织的信息，这可能导致不良的细胞统计。因此,对于可以在3D中的完整组织样本内提供详细的分子和细胞洞察的成像模态存在未满足的需要。使用GFP标记的GLUT4作为概念证明，我们在这里提出了一种新颖的光学介观方法，该方法可以精确测量完整小鼠心脏的超薄切片（5mmx5mmx3mm）中整个心肌特定解剖结构中GLUT4的空间位置。我们揭示了不同的GLUT4在心脏壁的分布模式，并强调了响应高脂肪饮食的GLUT4表达水平的具体变化，我们确定了表达模式中的性别依赖性差异。这种方法适用于任何可以标记为光学显微镜的目标，和其他复杂组织时，器官结构需要与细胞细节同时考虑。
