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葡萄糖氧化驱动躯干神经嵴细胞的发育和命运。

Glucose oxidation drives trunk neural crest cell development and fate.

机构信息

Université Paris-Est Créteil, INSERM, IMRB, 94010 Créteil, France.

Laboratoire Gly-CRRET, Université Paris-Est Créteil, 94000 Créteil, France.

出版信息

J Cell Sci. 2023 Aug 15;136(16). doi: 10.1242/jcs.260607.

DOI:10.1242/jcs.260607
PMID:37589341
Abstract

Bioenergetic metabolism is a key regulator of cellular function and signaling, but how it can instruct the behavior of cells and their fate during embryonic development remains largely unknown. Here, we investigated the role of glucose metabolism in the development of avian trunk neural crest cells (NCCs), a migratory stem cell population of the vertebrate embryo. We uncovered that trunk NCCs display glucose oxidation as a prominent metabolic phenotype, in contrast to what is seen for cranial NCCs, which instead rely on aerobic glycolysis. In addition, only one pathway downstream of glucose uptake is not sufficient for trunk NCC development. Indeed, glycolysis, mitochondrial respiration and the pentose phosphate pathway are all mobilized and integrated for the coordinated execution of diverse cellular programs, epithelial-to-mesenchymal transition, adhesion, locomotion, proliferation and differentiation, through regulation of specific gene expression. In the absence of glucose, the OXPHOS pathway fueled by pyruvate failed to promote trunk NCC adaptation to environmental stiffness, stemness maintenance and fate-decision making. These findings highlight the need for trunk NCCs to make the most of the glucose pathway potential to meet the high metabolic demands appropriate for their development.

摘要

生物能量代谢是细胞功能和信号转导的关键调节因子,但它如何在胚胎发育过程中指导细胞的行为和命运仍然知之甚少。在这里,我们研究了葡萄糖代谢在鸟类躯干神经嵴细胞(NCC)发育中的作用,这是脊椎动物胚胎中一种迁移的干细胞群体。我们发现,与颅 NCC 不同,躯干 NCC 表现出葡萄糖氧化作为一个突出的代谢表型,而颅 NCC 则依赖于有氧糖酵解。此外,葡萄糖摄取后的一条途径对于躯干 NCC 的发育是不够的。事实上,糖酵解、线粒体呼吸和戊糖磷酸途径都被动员和整合,以通过调节特定基因的表达来协调执行各种细胞程序,如上皮-间充质转化、黏附、迁移、增殖和分化。在没有葡萄糖的情况下,由丙酮酸驱动的 OXPHOS 途径未能促进躯干 NCC 适应环境硬度、维持干性和做出命运决策。这些发现强调了躯干 NCC 需要充分利用葡萄糖途径的潜力,以满足其发育所需的高代谢需求。

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