小鼠胚胎主动脉-性腺-中肾区与成年骨髓巨核细胞的分子特征分析

doi:10.19586/j.2095-2341.2025.0009

生物技术进展 ›› 2025, Vol. 15 ›› Issue (4): 702-710.DOI: 10.19586/j.2095-2341.2025.0009

• 研究论文 • 上一篇

小鼠胚胎主动脉-性腺-中肾区与成年骨髓巨核细胞的分子特征分析

蔡怡霏¹^,²(), 马叶子¹^,², 夏美娟¹^,², 刘翠翠¹^,², 王洪涛¹^,², 周家喜¹^,²()

^1.中国医学科学院血液病医院（中国医学科学院血液学研究所），血液与健康全国重点实验室，国家血液系统疾病临床医学研究中心，细胞生态海河实验室，天津 300020
^2.天津医学健康研究院，天津 301600

收稿日期:2025-02-01 接受日期:2025-03-19 出版日期:2025-07-25 发布日期:2025-09-08
通讯作者: 周家喜
作者简介:蔡怡霏 E-mail: caiyifei@ihcams.ac.cn；
基金资助:
国家自然面上基金项目(32271161);天津市科技计划项目-科技重大专项与工程(24ZXZSSS00080);中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-073);细胞生态海河实验室“揭榜挂帅”项目(22HHXBSS00031)

Analysis of Molecular Characteristics of Megakaryocytes Between Embryonic Aorta-gonad-mesonephros and Adult Bone Marrow

Yifei CAI¹^,²(), Yezi MA¹^,², Meijuan XIA¹^,², Cuicui LIU¹^,², Hongtao WANG¹^,², Jiaxi ZHOU¹^,²()

^1.State Key Laboratory of Experimental Hematology，National Clinical Research Center for Blood Diseases，Haihe Laboratory of Cell Ecosystem，Institute of Hematology & Blood Diseases Hospital，Chinese Academy of Medical Sciences & Peking Union Medical College，Tianjin 300020，China
^2.Tianjin Institutes of Health Science，Tianjin 301600，China

Received:2025-02-01 Accepted:2025-03-19 Online:2025-07-25 Published:2025-09-08
Contact: Jiaxi ZHOU

摘要/Abstract

摘要：

巨核细胞是主要存在于成年骨髓中、以产生血小板为主要功能的一类细胞，除此之外，成年期骨髓巨核细胞还具有维持造血干细胞（hematopoietic stem cells, HSC）稳态的作用。近年来研究发现，主动脉-性腺-中肾区（aorta-gonad-mesonephros, AGM）中也存在巨核细胞，并且其参与调控造血干细胞前体（pre-HSC）的产生及成熟。AGM区是最早产生HSC的部位，而骨髓是成年期HSC定居和造血的主要位点，巨核细胞是否在这2个位点通过不同的分子机制调控HSC的发育和功能尚不明确。基于近期报道的小鼠胚胎期AGM区巨核细胞及成年骨髓巨核细胞的单细胞转录组数据，对二者的整体分子特征以及调控HSC生物学过程相关的分子特征进行了对比分析。结果发现，小鼠AGM区巨核细胞与成年期骨髓巨核细胞的分子特征存在较大差异。其中，AGM区巨核细胞高表达细胞增殖、循环系统发育、干细胞发育及分化等分子特征；而成年骨髓巨核细胞高表达免疫反应、外界刺激应答、止凝血、细胞通讯等分子特征。此外，AGM区巨核细胞与成年骨髓巨核细胞高表达不同的与HSC调控相关的分子。研究结果提示，AGM区巨核细胞和成年期骨髓巨核细胞可能通过不同的功能分子调控HSC的发育及功能，可为研究胚胎期和成年期巨核细胞的功能差异及其分子机制提供理论依据。

关键词: 巨核细胞, 主动脉-性腺-中肾区, 骨髓, 造血干细胞, 单细胞转录组测序

Abstract:

Megakaryocytes are a type of cell primarily present in adult bone marrow， with the main function of producing platelets. In addition， adult bone marrow megakaryocytes also play a role in maintaining the homeostasis of hematopoietic stem cells （HSCs）. Recent studies have revealed that megakaryocytes also exist in the aorta-gonad-mesonephros （AGM） region and are involved in regulating the generation and maturation of hematopoietic stem cell precursors （pre-HSCs）. The AGM region is the earliest site for HSC production， while the bone marrow is the main site for HSC colonization and hematopoiesis in adulthood. However， it remains unclear whether megakaryocytes regulate HSC development and function through distinct molecular mechanisms at these two sites. Based on recently reported single-cell transcriptome data of megakaryocytes from the AGM region in mouse embryos and from adult bone marrow， we performed a comparative analysis of their overall molecular characteristics and the molecular features associated with regulating HSC biological processes. The results showed significant differences in molecular characteristics between AGM region megakaryocytes and adult bone marrow megakaryocytes in mice. Specifically， AGM region megakaryocytes highly expressed molecular features related to cell proliferation， circulatory system development， stem cell development， and differentiation； in contrast， adult bone marrow megakaryocytes highly expressed molecular features associated with immune response， response to external stimuli， hemostasis and coagulation， and cell communication. Furthermore， AGM region megakaryocytes and adult bone marrow megakaryocytes highly expressed different HSC regulation-related molecules. These findings suggested that megakaryocytes in the AGM region and adult bone marrow may regulate HSC development and function through distinct functional molecules， providing a theoretical basis for investigating the functional differences between embryonic and adult megakaryocytes and their underlying molecular mechanisms.

Key words: megakaryocytes, aorta-gonad-mesonephros, bone marrow, hematopoietic stem cells, single-cell transcrriptome

中图分类号:

Q291

蔡怡霏, 马叶子, 夏美娟, 刘翠翠, 王洪涛, 周家喜. 小鼠胚胎主动脉-性腺-中肾区与成年骨髓巨核细胞的分子特征分析[J]. 生物技术进展, 2025, 15(4): 702-710.

Yifei CAI, Yezi MA, Meijuan XIA, Cuicui LIU, Hongtao WANG, Jiaxi ZHOU. Analysis of Molecular Characteristics of Megakaryocytes Between Embryonic Aorta-gonad-mesonephros and Adult Bone Marrow[J]. Current Biotechnology, 2025, 15(4): 702-710.

图/表 6

表1 数据来源汇总

Table 1 Summary of data source

器官	物种	细胞类型	时期	细胞数目	测序方法	数据号	来源
主动脉-性腺-中肾区	小鼠	巨核细胞	胚胎（孕11.5 d）	209	Smart-seq2	GSE168224	[13]
骨髓	小鼠	巨核细胞	成年	851	Smart-seq2	OEP001128	[11]

图1 小鼠胚胎期AGM区和成年期骨髓巨核细胞分子特征分析注：差异基因表达热图展示小鼠AGM区和骨髓巨核细胞的整体差异基因表达情况。左侧显示二者各自上调的基因数；通过颜色及深浅表示基因表达丰度的高低，蓝色越深代表表达丰度越低，红色越深代表表达丰度越高。

Fig. 1 Analysis of molecular characteristics between megakaryocytes from mouse AGM and adult bone marrow

表2 小鼠胚胎期AGM区和成年期骨髓巨核细胞代表性生物学过程

Table 2 Representative biological processes of megakaryocytes from mouse embryonic AGM and adult bone marrow

	生物学过程	P值
主动脉-性腺-中肾区	细胞周期	2.40E-15
	循环系统发育	2.83E-15
	干细胞发育	1.63E-08
	干细胞分化	2.04E-06
骨髓	免疫系统反应	5.34E-32
	外界刺激反应	3.01E-26
	止凝血	2.36E-25
	细胞通讯	1.25E-16

图2 小鼠胚胎期AGM区的巨核细胞（相较于成年骨髓）的分子特征分析A~B：箱线图和小提琴图分别展示小鼠AGM区巨核细胞的细胞周期基因集的评分及其具体基因表达水平；C~D：箱线图和小提琴图分别展示小鼠AGM区巨核细胞的循环系统发育基因集的评分及其具体基因表达水平；E~F：箱线图和小提琴图分别展示小鼠AGM区巨核细胞的干细胞发育基因集的评分及其具体基因表达水平；G~H：箱线图和小提琴图分别展示小鼠AGM区巨核细胞的干细胞分化基因集的评分及其具体基因表达水平；通过Wilcoxon秩和检验计算得出P值，***表示差异在P<0.001水平有统计学意义

Fig. 2 Molecular characteristics analysis of megakaryocytes from mouse embryonic AGM (compared to adult bone marrow)

图3 小鼠成年期骨髓巨核细胞（相较于胚胎期AGM区）的分子特征分析A~B：箱线图和小提琴图分别展示小鼠骨髓巨核细胞的免疫系统反应基因集的评分及其具体基因表达水平；C~D：箱线图和小提琴图分别展示小鼠骨髓巨核细胞的外界刺激反应基因集的评分及其具体基因表达水平；E~F：箱线图和小提琴图分别展示小鼠骨髓巨核细胞的止凝血基因集的评分及其具体基因表达水平；G~H：箱线图和小提琴图分别展示小鼠骨髓巨核细胞的细胞通讯基因集的评分及其具体基因表达水平；通过Wilcoxon秩和检验计算得出P值，***表示在P<0.001水平有统计学差异

Fig. 3 Molecular characteristics analysis of megakaryocytes from mouse adult bone marrow (compared to embryonic AGM)

图4 小鼠胚胎期AGM区及成年期骨髓巨核细胞中涉及造血干细胞生物学过程的差异基因分析A：小提琴图展示小鼠胚胎期AGM区巨核细胞中，相较于成年期骨髓高表达的涉及造血干细胞生物学过程的基因表达水平；B：小提琴图展示小鼠成年期骨髓巨核细胞中，相较于胚胎期AGM区高表达的涉及造血干细胞生物学过程的基因表达水平

Fig. 4 Differential gene analysis of hematopoietic stem cell biological processes in mouse embryonic AGM and adult bone marrow derived megakaryocytes

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小鼠胚胎主动脉-性腺-中肾区与成年骨髓巨核细胞的分子特征分析

Analysis of Molecular Characteristics of Megakaryocytes Between Embryonic Aorta-gonad-mesonephros and Adult Bone Marrow

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