核转录因子NFYB和NFYC促进红系终末分化

doi:10.16352/j.issn.1001-6325.2022.06.006

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (6): 920-926.doi: 10.16352/j.issn.1001-6325.2022.06.006

核转录因子NFYB和NFYC促进红系终末分化

余东林, 杨希, 阴佳滢, 刘雪会^*, 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:2022-04-22 出版日期:2022-06-05 发布日期:2022-06-02
通讯作者: * lvxiang@pumc.edu.cn; liuxuehui@ibms.pumc.edu.cn
基金资助:
中国医学科学院创新工程(2021-I2M-1-019)

Nuclear transcription factors NFYB and NFYC promote terminal erythroid differentiation

YU Dong-lin, YANG Xi, YIN Jia-ying, LIU Xue-hui^*, LYU Xiang^*

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

Received:2022-03-28 Revised:2022-04-22 Online:2022-06-05 Published:2022-06-02
Contact: * lvxiang@pumc.edu.cn; liuxuehui@ibms.pumc.edu.cn

摘要/Abstract

摘要： 目的利用单细胞转录组数据分析挖掘红系终末分化的潜在转录因子,并重点对预测得到的核转录因子NFYB和NFYC在红系终末分化中的表达和功能进行探究。方法使用人骨髓红系终末分化单细胞转录组数据,结合SCENIC分析预测分化阶段特异性转录调控因子。利用公共测序数据集重点分析预测出的NFYB和NFYC在人与小鼠红系终末分化不同阶段中的表达;荧光激活细胞分选技术(FACS)分选小鼠胎肝体外红系终末分化各阶段的细胞,检测Nfyb和Nfyc的表达水平。在小鼠胎肝红系分化体系中使用慢病毒感染,分别敲低Nfyb和Nfyc,检测红系终末分化及脱核的变化。结果通过SCENIC分析预测出NFYB和NFYC是红系终末分化早期的调控因子,在人与小鼠的红系终末分化早期表达较高,晚期则降低。在小鼠胎肝体外红系分化体系中分别敲低Nfyb和Nfyc,均可显著抑制红系终末分化(P＜0.05)及脱核(P＜0.05)。结论 NFYB和NFYC促进红系终末分化过程。

关键词: NFYB, NFYC, SCENIC, 红系终末分化

Abstract: Objective To predict potential regulators of terminal erythroid differentiation by single-cell transcriptome data mining, and then focus on exploring the expression pattern and function of nuclear transcription factors NFYB and NFYC in terminal erythroid differentiation. Methods Using published single-cell transcriptome data of human terminal erythropoiesis, SCENIC analysis was performed to predict stage-specific transcription regulators. The expression levels of two predicted regulators, NFYB and NFYC, in different stages of human and mouse terminal erythropoiesis were first analyzed in public bulk RNA-seq data; cells among different stages of terminal erythroid differentiation in mouse fetal liver were sorted by flow cytometry, NFYB and NFYC expression levels were then detected by RT-qPCR. In addition, the expression of NFYB and NFYC was inhibited by lentivirus-mediated shRNA interference and the efficiency of terminal erythroid differentiation and enucleation was examined. Results NFYB and NFYC were potential regulators at early stage of terminal erythropoiesis by SCENIC analysis. Their expression level was high at early stage of both human and mouse terminal erythropoiesis and then decreased at the last stage. Knockdown of Nfyb and Nfyc in mouse fetal liver derived erythroid cells significantly inhibited terminal erythroid differentiation and enucleation (P＜0.05). Conclusions NFYB and NFYC promote the terminal erythroid differentiation.

Key words: NFYB, NFYC, SCENIC, terminal erythropoiesis

中图分类号:

余东林, 杨希, 阴佳滢, 刘雪会, 吕湘. 核转录因子NFYB和NFYC促进红系终末分化[J]. 基础医学与临床, 2022, 42(6): 920-926.

YU Dong-lin, YANG Xi, YIN Jia-ying, LIU Xue-hui, LYU Xiang. Nuclear transcription factors NFYB and NFYC promote terminal erythroid differentiation[J]. Basic & Clinical Medicine, 2022, 42(6): 920-926.

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核转录因子NFYB和NFYC促进红系终末分化

Nuclear transcription factors NFYB and NFYC promote terminal erythroid differentiation

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