造血干细胞发育过程中的信号通路调控

doi:10.16288/j.yczz.21-026

遗传 ›› 2021, Vol. 43 ›› Issue (4): 295-307.doi: 10.16288/j.yczz.21-026

造血干细胞发育过程中的信号通路调控

张春霞^1,², 刘峰¹()

^1. 中国科学院动物研究所,膜生物学国家重点实验室,北京 100101
^2. 波士顿儿童医院,波士顿 02115

收稿日期:2021-01-20 修回日期:2021-03-01 出版日期:2021-04-16 发布日期:2021-03-15
通讯作者: 刘峰 E-mail:liuf@ioz.ac.cn
作者简介:张春霞,博士,研究方向：造血干细胞发育。E-mail: zhangchxa@163.com
2010—2017年就读于中国科学院动物研究所,在血液与心血管发育研究组攻读博士学位,目前在美国哈佛医学院/波士顿儿童医院做博士后。博士期间,主要研究斑马鱼造血干细胞发育的调控机制,阐明了BMP与ERK信号通路在造血干细胞产生过程中的相互关联(Nat Commun, 2014年),发现了炎性信号通路可以通过Notch信号来调控造血干细胞的产生(Blood, 2015年),首次揭示了m⁶A修饰在胚胎造血干细胞命运决定中的关键作用(Nature, 2017年)。这些工作不仅增加了人们对造血干细胞产生机制的认识,而且对体外诱导扩增造血干细胞提供了理论指导。博士论文《BMP-ERK信号通路以及炎性信号调控斑马鱼造血干细胞产生的分子机制》获得2020年中国科学院优秀博士生论文。
基金资助:
国家重点研发计划项目编号(2018YFA0800200);国家重点研发计划项目编号(2018YFA080100);中国科学院战略性科技先导专项编号(XDA16010207);国家自然科学基金重点项目资助编号(32030032);国家自然科学基金重点项目资助编号(31830061)

Regulatory signaling pathways in hematopoietic stem cell development

Zhang Chunxia^1,², Liu Feng¹()

^1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
^2. Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, Massachusetts 02115, USA;

Received:2021-01-20 Revised:2021-03-01 Online:2021-04-16 Published:2021-03-15
Contact: Liu Feng E-mail:liuf@ioz.ac.cn
Supported by:
Supported by the National Key Research and Development Program of China Nos(2018YFA0800200);Supported by the National Key Research and Development Program of China Nos(2018YFA080100);the Strategic Priority Research Program of the Chinese Academy of Sciences, China No(XDA16010207);the National Natural Science Foundation of China (Nos)(32030032);the National Natural Science Foundation of China (Nos)(31830061)

摘要/Abstract

摘要：

血液系统是维持机体生命活动最重要的系统之一,为机体提供所需的氧气和营养物质,通过物质交换维持内环境的稳态,同时为机体提供免疫防御与保护。血细胞是血液的重要组成成分,机体中成熟血细胞类型起源于具有自我更新及分化潜能的多能成体干细胞—造血干细胞(hematopoietic stem cells, HSCs)。造血干细胞及各类血细胞产生、发育及成熟的过程称为造血过程,该过程开始于胚胎发育早期并贯穿整个生命过程,任一阶段出现异常都可能导致血液疾病的发生。因此,深入探究造血发育过程及其调控机制对于认识并治疗血液疾病至关重要。近年来,以小鼠(Mus musculus)和斑马鱼(Danio rerio)作为动物模型来研究造血发育取得了一系列的进展。其中,BMP、Notch和Wnt等信号通路对造血干细胞的命运决定和产生发挥了重要作用。本文对这些信号通路在小鼠和斑马鱼造血过程中的调控作用进行系统总结,以期能够完善造血发育过程的调控网络并为临床应用提供指导。

关键词: 造血干细胞, 信号通路, BMP, Notch, Wnt

Abstract:

The blood system provides the body with oxygen and nutrients, maintains the homeostasis of the internal environment through material exchange, and keeps the body with immune defense and protection. Hematopoietic stem cells (HSCs), which are pluripotent adult stem cells with self-renewal and differentiation potential, are the origin of mature blood cells in the body. The production, development and maturation processes of HSCs and their derivatives are the so-called ‘hematopoiesis’, which begins in the early embryonic development and throughout the life course; any abnormality during these processes can cause the occurrence of hematological diseases. Therefore, a deeper understanding of hematopoietic development and its regulation is important to the diagnosis and treatment of blood diseases. In recent years, a series of advances have been made in studying hematopoietic development using mice and zebrafish as animal models. It has been shown that BMP, Notch and Wnt signaling pathways play an important role in the fate determination and generation of HSCs. In this review, we systematically summarize the regulatory roles of these signaling pathways in the hematopoietic process of mice and zebrafish embryos, to improve our understanding on the underlying regulatory network of hematopoietic development and provide guidance for clinical application.

Key words: hematopoietic stem cell, signaling pathways, BMP, Notch, Wnt

张春霞, 刘峰. 造血干细胞发育过程中的信号通路调控[J]. 遗传, 2021, 43(4): 295-307.

Zhang Chunxia, Liu Feng. Regulatory signaling pathways in hematopoietic stem cell development[J]. Hereditas(Beijing), 2021, 43(4): 295-307.

图/表 1

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造血干细胞发育过程中的信号通路调控

Regulatory signaling pathways in hematopoietic stem cell development

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