Spatiotemporal Analysis of a Glycolytic Activity Gradient Linked to Mouse Embryo Mesoderm Development.
Spatiotemporal Analysis of a Glycolytic Activity Gradient Linked to Mouse Embryo Mesoderm Development.
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DOI：
10.1016/j.devcel.2017.01.015
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发表时间：
2017-02-27
影响因子：
11.8
通讯作者：
Aulehla A
中科院分区：
文献类型：
--
作者：
Bulusu V;Prior N;Snaebjornsson MT;Kuehne A;Sonnen KF;Kress J;Stein F;Schultz C;Sauer U;Aulehla A
在胚胎发育过程中，新陈代谢是如何重新连接的，这在很大程度上仍然是未知的，因为它仍然是一个主要的技术挑战，以时空分辨率来解决代谢活动或代谢物水平。在这里，我们研究了器官发生阶段小鼠胚胎发育过程中的代谢变化，重点是前体中胚层（PSM）。我们测量了糖酵解标记动力学13 C-葡萄糖示踪实验，并检测到升高的糖酵解后，更未分化的PSM。我们发现的证据表明，空间代谢的差异是功能相关的PSM发展过程中。为了能够实时定量的糖酵解代谢产物的时空分辨率，我们产生了丙酮酸FRET传感器报告小鼠线。我们揭示了动态变化的细胞溶质丙酮酸水平的细胞过渡到一个更前PSM状态。结合，我们的方法确定了整个PSM的糖酵解活性的梯度，我们提供的证据表明，这些时空代谢变化与PSM的发展和分化有着内在的联系。实时成像揭示丙酮酸梯度动力学代谢状态与前体中胚层细胞分化有关Bulusu，Prior，Snaebjoernsson et al.在小鼠胚胎中，在有丝分裂前中胚层（PSM）发育过程中确定糖酵解活性梯度。使用FRET-丙酮酸传感器小鼠模型对代谢物水平进行实时成像，他们发现空间代谢差异在功能上与PSM细胞分化和发育相关，并且与PSM细胞分化和发育有内在联系。
How metabolism is rewired during embryonic development is still largely unknown, as it remains a major technical challenge to resolve metabolic activities or metabolite levels with spatiotemporal resolution. Here, we investigated metabolic changes during development of organogenesis-stage mouse embryos, focusing on the presomitic mesoderm (PSM). We measured glycolytic labeling kinetics from 13C-glucose tracing experiments and detected elevated glycolysis in the posterior, more undifferentiated PSM. We found evidence that the spatial metabolic differences are functionally relevant during PSM development. To enable real-time quantification of a glycolytic metabolite with spatiotemporal resolution, we generated a pyruvate FRET-sensor reporter mouse line. We revealed dynamic changes in cytosolic pyruvate levels as cells transit toward a more anterior PSM state. Combined, our approach identifies a gradient of glycolytic activity across the PSM, and we provide evidence that these spatiotemporal metabolic changes are intrinsically linked to PSM development and differentiation. Identification of glycolytic activity gradient in mouse presomitic mesoderm Development of a pyruvate FRET-reporter mouse model Real-time imaging reveals pyruvate gradient dynamics Metabolic state is linked to presomitic mesoderm cell differentiation Bulusu, Prior, Snaebjoernsson et al. identify a glycolytic activity gradient in the mouse embryo during presomitic mesoderm (PSM) development. Using a FRET-pyruvate sensor mouse model for real-time imaging of metabolite levels, they find that spatial metabolic differences are functionally relevant and intrinsically linked to PSM cell differentiation and development.