Nekooie Marnany Nioosha, Dady Alwyn, Duband-Goulet Isabelle, Relaix Frédéric, Motterlini Roberto, Foresti Roberta, Dufour Sylvie, Duband Jean-Loup
Institut Mondor de Recherches Biomédicales, Faculté de Santé, INSERM, Université Paris-Est Créteil, 94000, Créteil, France.
Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT, 84112, USA.
Nat Commun. 2025 Jul 1;16(1):5554. doi: 10.1038/s41467-025-58573-0.
Metabolic reprograming has been linked to epithelial-to-mesenchymal transition (EMT) in cancer cells, but how it influences EMT in normal cells remains largely unknown. Here we explored how metabolism impacts delamination and migration of avian trunk neural crest cells, an important progenitor cell population of the vertebrate embryo. We report that delamination exhibits a quiescent metabolic phenotype whereas migration is characterized by OXPHOS-driven metabolism coupled to distinct expression of metabolic, EMT and developmental genes. While glucose and glutamine are required for delamination and migration, we uncover a specific role for glutamine and its catabolizing enzyme glutaminase in the unfolding of NCC delamination. Namely, glutamine is required for nuclear accumulation of glutaminase, which interacts and cooperates with Wnt signaling to regulate EMT gene expression and cell cycle during delamination. Our data indicate that similarly to cancer cells, embryonic cells engage metabolic enzymes for non-canonical signaling functions to connect metabolism with EMT.
代谢重编程已被证明与癌细胞的上皮-间质转化（EMT）有关，但它如何影响正常细胞中的EMT在很大程度上仍不清楚。在这里，我们探究了代谢如何影响鸟类躯干神经嵴细胞的分层和迁移，这是脊椎动物胚胎中一个重要的祖细胞群体。我们报告称，分层表现出静止的代谢表型，而迁移的特征是由氧化磷酸化驱动的代谢，并伴随着代谢、EMT和发育基因的不同表达。虽然分层和迁移都需要葡萄糖和谷氨酰胺，但我们发现谷氨酰胺及其分解代谢酶谷氨酰胺酶在神经嵴细胞分层过程中发挥着特定作用。具体而言，谷氨酰胺是谷氨酰胺酶核积累所必需的，谷氨酰胺酶与Wnt信号相互作用并协同调节分层过程中的EMT基因表达和细胞周期。我们的数据表明，与癌细胞类似，胚胎细胞利用代谢酶发挥非经典信号功能，将代谢与EMT联系起来。
