蛋白酪氨酸磷酸酶4A3(PTP4A3)促进小鼠胎肝来源红系细胞脱核

doi:10.16352/j.issn.1001-6325.2022.07.1026

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (7): 1026-1030.doi: 10.16352/j.issn.1001-6325.2022.07.1026

蛋白酪氨酸磷酸酶4A3(PTP4A3)促进小鼠胎肝来源红系细胞脱核

胡欣俊, 余东林, 范宏, 韩改净, 薛征^*, 吕湘^*

中国医学科学院基础医学研究所北京协和医学院基础学院病理生理学系医学分子生物学国家重点实验室,北京 100005

收稿日期:2022-03-28 修回日期:2022-04-27 出版日期:2022-07-05 发布日期:2022-06-29
通讯作者: * lvxiang@pumc.edu.cn; xuezheng@ibms.pumc.edu.cn
基金资助:
国家自然科学基金(82170120)

Protein tyrosine phosphatase 4A3(PTP4A3) promotes enucleation in mouse fetal liver-derived erythroid cells

HU Xin-jun, YU Dong-lin, FAN Hong, HAN Gai-jing, XUE Zheng^*, LYU Xiang^*

State Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005

Received:2022-03-28 Revised:2022-04-27 Online:2022-07-05 Published:2022-06-29
Contact: * lvxiang@pumc.edu.cn; xuezheng@ibms.pumc.edu.cn

摘要/Abstract

摘要： 目的探索在小鼠胎肝来源红系细胞中蛋白酪氨酸磷酸酶4A3(PTP4A3)在红系终末分化和脱核中的作用及分子机制。方法 RT-qPCR检测Ptp4a3在终末分化过程中的表达情况。利用短发夹RNA(shRNA)干扰技术在小鼠胎肝诱导红系分化体系中敲低Ptp4a3的表达,流式细胞分选GFP阳性细胞后RT-qPCR验证其敲低效率,流式细胞测量术分析检测Ptp4a3敲低后对红系分化和脱核的影响。RNA表达谱测序并分析在红系细胞终末分化过程中Ptp4a3敲低影响的通路和基因。结果 PTP4A3在红系细胞终末分化过程中表达水平逐渐升高。在小鼠胎肝来源红系细胞中成功敲低Ptp4a3的表达,流式细胞测量术检测发现敲低Ptp4a3可显著降低红系细胞脱核率(P＜0.05)。表达谱分析发现敲低Ptp4a3影响红系终末分化过程中细胞周期相关基因表达。结论 PTP4A3在红系细胞终末分化晚期高表达,并参与调控细胞脱核过程。

关键词: 蛋白酪氨酸磷酸酶4A3, 红系终末分化, 红系脱核, 细胞周期

Abstract: Objective To investigate the expression and function of protein tyrosine phosphatase 4A3(PTP4A3) in terminal erythroid differentiation and underlying molecular mechanism. Methods RT-qPCR was used to detect the expression of Ptp4a3 during terminal differentiation. Knockdown of Ptp4a3 expression in mouse fetal liver induced erythroid differentiation system by short hairpin RNA(shRNA) interference, the knockdown efficiency was verified by RT-qPCR after GFP positive cells were sorted by flow cytometry, and the effect of Ptp4a3 knockdown on erythroid differentiation and enucleation was detected by flow cytometry. Transcriptional profiling was performed to explore the potential downstream pathways of Ptp4a3. Results Ptp4a3 was among the top 100 ranked expressing genes during mouse terminal erythroid differentiation, and its expression gradually increased following the differentiation process. In mouse fetal liver-derived erythroid cells, Ptp4a3 was successfully knocked down by shRNA interference. Flow cytometry analysis showed that Ptp4a3 knockdown significantly decreased the proportion of enucleated erythrocytes(P＜0.05). Transcriptome analysis revealed that Ptp4a3 knockdown resulted in upregulation of cell cycle-related genes. Conclusions PTP4A3 is highly expressed in late stage of terminal erythroid differentiation. Knockdown Ptp4a3 significantly reduces enucleation erythroid of cells.

Key words: protein tyrosine phosphatase 4A3, terminal erythroid differentiation, erythroid enucleation, cell cycle

中图分类号:

胡欣俊, 余东林, 范宏, 韩改净, 薛征, 吕湘. 蛋白酪氨酸磷酸酶4A3(PTP4A3)促进小鼠胎肝来源红系细胞脱核[J]. 基础医学与临床, 2022, 42(7): 1026-1030.

HU Xin-jun, YU Dong-lin, FAN Hong, HAN Gai-jing, XUE Zheng, LYU Xiang. Protein tyrosine phosphatase 4A3(PTP4A3) promotes enucleation in mouse fetal liver-derived erythroid cells[J]. Basic & Clinical Medicine, 2022, 42(7): 1026-1030.

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蛋白酪氨酸磷酸酶4A3(PTP4A3)促进小鼠胎肝来源红系细胞脱核

Protein tyrosine phosphatase 4A3(PTP4A3) promotes enucleation in mouse fetal liver-derived erythroid cells

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