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维生素C衍生物/AA2P通过上调……促进红细胞分化。

Vitamin C derivative/AA2P promotes erythroid differentiation by upregulating .

作者信息

Tan Xiaoyu, Li Meng, Liang Yue, Ruan Xiuyan, Zhang Zhaojun, Fang Xiangdong

机构信息

Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing 100101, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Life Med. 2023 Nov 13;2(5):lnad043. doi: 10.1093/lifemedi/lnad043. eCollection 2023 Oct.

Abstract

Vitamin C is used to treat anaemia; however, the mechanism through which vitamin C promotes erythroid differentiation is not comprehensively understood. The erythroid differentiation induction system can reveal the differentiation mechanism and provide erythrocytes for clinical transfusion and anaemia treatment. This process can be promoted by adding small-molecule compounds. In this study, we added l-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AA2P), a derivative of vitamin C, to an erythroid differentiation system induced from umbilical cord blood haematopoietic stem and progenitor cells and detected its effect on erythroid differentiation using single-cell transcription sequencing technology combined with non-targeted metabolism detection. AA2P increased the proportion of late basophilic erythroblasts, upregulating the expression of erythroid-related regulatory molecules GATA1, KLF1, ALAS2, and the globins HBG and HBB. is a target gene of AA2P, and knockdown affected the expression of globin-related genes. AA2P also increased glycolysis and decreased oxidative phosphorylation to facilitate terminal erythroid differentiation and enhanced the proliferation of early erythroid progenitors by altering the cell cycle. These results provide a reliable basis for using vitamin C to improve the efficiency of erythropoiesis and for the clinical treatment of anaemia.

摘要

维生素C用于治疗贫血;然而,维生素C促进红系分化的机制尚未完全明确。红系分化诱导系统能够揭示分化机制,并为临床输血和贫血治疗提供红细胞。添加小分子化合物可促进这一过程。在本研究中,我们将维生素C的衍生物l-抗坏血酸2-磷酸倍半镁盐水合物(AA2P)添加到由脐带血造血干细胞和祖细胞诱导的红系分化系统中,并结合非靶向代谢检测,使用单细胞转录测序技术检测其对红系分化的影响。AA2P增加了晚期嗜碱性成红细胞的比例,上调了红系相关调控分子GATA1、KLF1、ALAS2以及珠蛋白HBG和HBB的表达。 是AA2P的靶基因,敲低该基因会影响珠蛋白相关基因的表达。AA2P还增加糖酵解并降低氧化磷酸化,以促进红系终末分化,并通过改变细胞周期增强早期红系祖细胞的增殖。这些结果为利用维生素C提高红细胞生成效率及贫血的临床治疗提供了可靠依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e8f/11749482/4151b3adad8e/lnad043_fig1.jpg

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