He Xinrong, Geng Zixiang, Zou Gang, Cui Zeyu, Wang Yu, Song Jiamin, Zhang Jing, Shao Yiye, Feng Jingtao, Wu Yuncheng, Liu Te, Zhu Xiaoying
Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Stem Cells Dev. 2025 Feb;34(3-4):85-98. doi: 10.1089/scd.2024.0160. Epub 2024 Dec 20.
Ninety-nine percent of alpha-synuclein (α-syn) in the human body is distributed in erythrocytes. However, the role that α-syn plays in erythropoiesis remains unclear. To determine the effect of α-syn on erythroid differentiation, the erythroid cells, derived from human CD34+ progenitors in the umbilical cord, were cultured in a system composed of a series of cytokines and harvested after 6 days. Our work showed α-syn inhibition-promoted erythropoiesis as characterized by altered activity of surface markers of erythroid development such as CD49d, CD36, and CD71; and different methylation status of GDP-D-mannose dehydratase, aldolase fructose-bisphosphate A, and sorbitol dehydrogenase, key enzymes involved in fructose and mannose metabolism. Reduced adenosine triphosphate and elevated lactic acid also suggested a shift in cellular metabolism from mitochondrial respiration to glycolysis. Our study revealed a previously unknown role for α-syn as a methylation regulator that alters the activity of key enzymes of the fructose and mannose metabolism, thus contributing to erythropoiesis.
人体中99%的α-突触核蛋白（α-syn）分布于红细胞中。然而，α-syn在红细胞生成中所起的作用仍不清楚。为了确定α-syn对红系分化的影响，将源自人脐带血CD34+祖细胞的红系细胞在由一系列细胞因子组成的体系中培养，并在6天后收获。我们的研究表明，α-syn抑制促进了红细胞生成，其特征为红系发育表面标志物（如CD49d、CD36和CD71）的活性改变；以及参与果糖和甘露糖代谢的关键酶——GDP-D-甘露糖脱水酶、果糖-1,6-二磷酸醛缩酶A和山梨醇脱氢酶的甲基化状态不同。三磷酸腺苷减少和乳酸升高也表明细胞代谢从线粒体呼吸向糖酵解转变。我们的研究揭示了α-syn作为一种甲基化调节因子的先前未知作用，它改变了果糖和甘露糖代谢关键酶的活性，从而促进红细胞生成。
