Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Institute of Imaging and Computer Vision, RWTH Aachen University, Aachen, Germany.
Nat Commun. 2021 Sep 10;12(1):5363. doi: 10.1038/s41467-021-25714-0.
The activity of epiphyseal growth plates, which drives long bone elongation, depends on extensive changes in chondrocyte size and shape during differentiation. Here, we develop a pipeline called 3D Morphometric Analysis for Phenotypic significance (3D MAPs), which combines light-sheet microscopy, segmentation algorithms and 3D morphometric analysis to characterize morphogenetic cellular behaviors while maintaining the spatial context of the growth plate. Using 3D MAPs, we create a 3D image database of hundreds of thousands of chondrocytes. Analysis reveals broad repertoire of morphological changes, growth strategies and cell organizations during differentiation. Moreover, identifying a reduction in Smad 1/5/9 activity together with multiple abnormalities in cell growth, shape and organization provides an explanation for the shortening of Gdf5 KO tibias. Overall, our findings provide insight into the morphological sequence that chondrocytes undergo during differentiation and highlight the ability of 3D MAPs to uncover cellular mechanisms that may regulate this process.
骺板的活性驱动长骨的伸长，这依赖于软骨细胞在分化过程中大小和形状的广泛变化。在这里，我们开发了一个称为表型意义的 3D 形态计量分析（3D MAPs）的管道，它结合了光片显微镜、分割算法和 3D 形态计量分析，以在保持生长板空间背景的同时，描述形态发生细胞行为。使用 3D MAPs，我们创建了一个包含数十万软骨细胞的 3D 图像数据库。分析揭示了分化过程中广泛的形态变化、生长策略和细胞组织。此外，鉴定出 Smad1/5/9 活性的降低以及细胞生长、形状和组织的多种异常，为 Gdf5 KO 胫骨缩短提供了一种解释。总的来说，我们的研究结果提供了对软骨细胞在分化过程中经历的形态学序列的深入了解，并强调了 3D MAPs 揭示可能调节这一过程的细胞机制的能力。
