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单细胞水平下的植入后小鼠发育的全胚胎成像和重建。

In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level.

机构信息

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.

出版信息

Cell. 2018 Oct 18;175(3):859-876.e33. doi: 10.1016/j.cell.2018.09.031. Epub 2018 Oct 11.

DOI:10.1016/j.cell.2018.09.031
PMID:30318151
Abstract

The mouse embryo has long been central to the study of mammalian development; however, elucidating the cell behaviors governing gastrulation and the formation of tissues and organs remains a fundamental challenge. A major obstacle is the lack of live imaging and image analysis technologies capable of systematically following cellular dynamics across the developing embryo. We developed a light-sheet microscope that adapts itself to the dramatic changes in size, shape, and optical properties of the post-implantation mouse embryo and captures its development from gastrulation to early organogenesis at the cellular level. We furthermore developed a computational framework for reconstructing long-term cell tracks, cell divisions, dynamic fate maps, and maps of tissue morphogenesis across the entire embryo. By jointly analyzing cellular dynamics in multiple embryos registered in space and time, we built a dynamic atlas of post-implantation mouse development that, together with our microscopy and computational methods, is provided as a resource. VIDEO ABSTRACT.

摘要

鼠胚胎一直是哺乳动物发育研究的核心;然而,阐明指导原肠胚形成和组织器官形成的细胞行为仍然是一个基本挑战。一个主要的障碍是缺乏能够系统地跟踪整个胚胎发育过程中细胞动态的活体成像和图像分析技术。我们开发了一种适用于大小、形状和光学特性在植入后鼠胚胎中急剧变化的光片显微镜,并以细胞水平捕获其从原肠胚形成到早期器官发生的发育过程。我们还开发了一种计算框架,用于重建长期细胞轨迹、细胞分裂、动态命运图谱以及整个胚胎组织形态发生图谱。通过联合分析在空间和时间上注册的多个胚胎中的细胞动力学,我们构建了一个具有植入后鼠发育的动态图谱,该图谱与我们的显微镜和计算方法一起作为资源提供。视频摘要。

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