中国科学院动物研究所黄仕强等研究人员合作发现，乙酰辅酶A代谢维持组蛋白乙酰化来促进人胎盘滋养层干细胞的合胞化。2024年7月30日，国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

研究人员使用了人类早期妊娠胎盘样本和人类滋养层干细胞（hTSC），发现葡萄糖代谢在hTSC和细胞滋养层细胞中高度活跃，但在合胞化过程中，葡萄糖代谢下降至基础水平，然而仍然是供能乙酰辅酶A和维持分化潜力所必需的。乙酸盐补充可以通过补充乙酰辅酶A和维持组蛋白乙酰化来挽救由于糖酵解不足而导致的合胞滋养层细胞融合，从而恢复合胞化基因的激活。

即使是短暂的糖酵解不足也可以永久性地抑制分化潜力并促进炎症，这也可以通过体内短暂的乙酸盐补充来永久性恢复。这些结果表明，hTSC在合胞化过程中仅保留基础糖酵解乙酰辅酶A代谢，通过营养响应的组蛋白乙酰化来调控细胞命运，这对于人们理解胎盘和胎儿营养之间的平衡具有重要意义。

据悉，在怀孕期间，胎盘-胎儿营养分配对于胎儿和母体健康至关重要。然而，胎盘滋养层细胞中营养代谢和分配的调控机制仍不清楚。

附：英文原文

Title: Acetyl-CoA metabolism maintains histone acetylation for syncytialization of human placental trophoblast stem cells

Author: Xin Yu, Hao Wu, Jiali Su, Xupeng Liu, Kun Liang, Qianqian Li, Ruoxuan Yu, Xuan Shao, Hongmei Wang, Yan-Ling Wang, Ng Shyh-Chang

Issue&Volume: 2024-07-30

Abstract: During pregnancy, placental-fetal nutrient allocation is crucial for fetal and maternalhealth. However, the regulatory mechanisms for nutrient metabolism and allocationin placental trophoblasts have remained unclear. Here, we used human first-trimesterplacenta samples and human trophoblast stem cells (hTSCs) to discover that glucosemetabolism is highly active in hTSCs and cytotrophoblasts, but during syncytialization,it decreases to basal levels, remaining necessary for fueling acetyl-CoA and differentiationpotential. Acetate supplementation could rescue syncytiotrophoblast fusion from glycolysisdeficiency by replenishing acetyl-CoA and maintaining histone acetylation, thus rescuingthe activation of syncytialization genes. Even brief glycolysis deficiency could permanentlyinhibit differentiation potential and promote inflammation, which could also be permanentlyrescued by brief acetate supplementation in vivo. These results suggest that hTSCs retain only basal glycolytic acetyl-CoA metabolismduring syncytialization to regulate cell fates via nutrient-responsive histone acetylation,with implications for our understanding of the balance between placental and fetalnutrition.

DOI: 10.1016/j.stem.2024.07.003

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00253-4