Department of Biochemistry, University of Washington, Seattle, WA, USA; Program in Molecular and Cellular Biology, University of Washington School of Medicine, Seattle, WA, USA.
Department of Biochemistry, University of Washington, Seattle, WA, USA.
Cell Rep. 2022 Oct 25;41(4):111552. doi: 10.1016/j.celrep.2022.111552.
A fundamental step in regeneration is rapid growth to replace lost tissue. Cells must generate sufficient lipids, nucleotides, and proteins to fuel rapid cell division. To define metabolic pathways underlying regenerative growth, we undertake a multimodal investigation of metabolic reprogramming in Xenopus tropicalis appendage regeneration. Regenerating tissues have increased glucose uptake; however, inhibition of glycolysis does not decrease regeneration. Instead, glucose is funneled to the pentose phosphate pathway (PPP), which is essential for full tail regeneration. Liquid chromatography-mass spectrometry (LC-MS) metabolite profiling reveals increased nucleotide and nicotinamide intermediates required for cell division. Using single-cell RNA sequencing (scRNA-seq), we find that highly proliferative cells have increased transcription of PPP enzymes and not glycolytic enzymes. Further, PPP inhibition results in decreased cell division specifically in regenerating tissue. Our results inform a model wherein regenerating tissues direct glucose toward the PPP, yielding nucleotide precursors to drive regenerative cell proliferation.
再生的一个基本步骤是快速生长以替代丢失的组织。细胞必须产生足够的脂质、核苷酸和蛋白质来为快速细胞分裂提供燃料。为了确定再生生长所依赖的代谢途径，我们对非洲爪蟾附肢再生中的代谢重编程进行了多模式研究。再生组织的葡萄糖摄取增加；然而，抑制糖酵解并不会减少再生。相反，葡萄糖被引导到戊糖磷酸途径（PPP），这对于完全的尾巴再生是必不可少的。液相色谱-质谱（LC-MS）代谢物分析显示，细胞分裂所需的核苷酸和烟酰胺中间产物增加。使用单细胞 RNA 测序（scRNA-seq），我们发现高度增殖的细胞中转录 PPP 酶的水平增加，而不是糖酵解酶。此外，PPP 抑制会导致再生组织中的细胞分裂减少。我们的结果提供了一个模型，其中再生组织将葡萄糖导向 PPP，产生核苷酸前体来驱动再生细胞增殖。
