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学科主题: 基础医学
题名:
Interleukin-3 promotes hemangioblast development in mouse aorta-gonad-mesonephros region
作者: He, Wen-Yan1,2; Lan, Yu3; Yao, Hui-Yu1; Li, Zhuan2; Wang, Xiao-Yan1; Li, Xiu-Sen1; Zhang, Ji-Yan4; Zhang, Yu5; Liu, Bing2; Mao, Ning1
关键词: interleukin-3 ; hemangioblast ; AGM ; definitive hematopoiesis ; hematopoietic stem cells
刊名: HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
发表日期: 2010-06-01
DOI: 10.3324/haematol.2009.014241
卷: 95, 期:6, 页:875-883
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology
研究领域[WOS]: Hematology
关键词[WOS]: HEMATOPOIETIC STEM-CELLS ; IN-VITRO ; EMBRYONIC-DEVELOPMENT ; MESODERMAL TISSUES ; DORSAL AORTA ; FETAL LIVER ; YOLK-SAC ; DIFFERENTIATION ; ENDOTHELIUM ; COMMITMENT
英文摘要:

Background

The hemangioblast is a bi-potential precursor cell with the capacity to differentiate into hematopoietic and vascular cells. In mouse E7.0-7.5 embryos, the hemangioblast can be identified by a clonal blast colony-forming cell (BL-CFC) assay or single cell OP9 co-culture. However, the ontogeny of the hemangioblast in mid-gestation embryos is poorly defined.

Design and Methods

The BL-CFC assay and the OP9 system were combined to illustrate the hemangioblast with lymphomyeloid and vascular potential in the mouse aorta-gonad-mesonephros region. The colony-forming assay, reverse transcriptase polymerase chain reaction analysis, immunostaining and flow cytometry were used to identify the hematopoietic potential, and Matrigel- or OP9-based methods were employed to evaluate endothelial progenitor activity.

Results

Functionally, the aorta-gonad-mesonephros-derived BL-CFC produced erythroid/myeloid progenitors, CD19(+) B lymphocytes, and CD3(+)TCR beta(+). T lymphocytes. Meanwhile, the BL-CFC-derived adherent cells generated CD31(+) tube-like structures on OP9 stromal cells, validating the endothelial progenitor potential. The aorta-gonad-mesonephros-derived hemangioblast was greatly enriched in CD31(+), endomucin(+) and CD105(+) subpopulations, which collectively pinpoints the endothelial layer as the main location. Interestingly, the BL-CFC was not detected in yolk sac, placenta, fetal liver or embryonic circulation. Screening of candidate cytokines revealed that interleukin-3 was remarkable in expanding the BL-CFC in a dose-dependent manner through the JAK2/STAT5 and MAPK/ERK pathways. Neutralizing interleukin-3 in the aorta-gonad-mesonephros region resulted in reduced numbers of BL-CFC, indicating the physiological requirement for this cytokine. Both hematopoietic and endothelial differentiation potential were significantly increased in interleukin-3-treated BL-CFC, suggesting a persistent positive influence. Intriguingly, interleukin-3 markedly amplified primitive erythroid and macrophage precursors in E7.5 embryos. Quantitative polymerase chain reaction analysis demonstrated declined Flk-1 and elevated Scl and von Willebrand factor transcription upon interleukin-3 stimulation, indicating accelerated hemangiopoiesis.

Conclusions

The hemangioblast with lymphomyeloid potential is one of the precursors of definitive hematopoiesis in the mouse aorta-gonad-mesonephros region. Interleukin-3 has a regulatory role with regards to both the number and capacity of the dual-potential hemangioblast.

语种: 英语
所属项目编号: 30730043 ; 30770921 ; 30871437 ; 30800427 ; 2005CB522705 ; 2005CB522506 ; 2006CB943601 ; 2007AA021109 ; 5092024 ; SKLP-Y200807
项目资助者: National Natural Science Foundation ; National Key Basic Research Program of China ; National 863 program ; Beijing Natural Science Foundation ; State Key Laboratory
WOS记录号: WOS:000279051100006
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51930
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Inst Basic Med Sci, Dept Cell Biol, Beijing 100850, Peoples R China
2.Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China
3.Acad Mil Med Sci, Affiliated Hosp, Lab Oncol, Beijing 100071, Peoples R China
4.Inst Biotechnol, State Key Lab Prote, Genet Lab Dev & Dis, Beijing, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Dept Immunol, Beijing 100871, Peoples R China

Recommended Citation:
He, Wen-Yan,Lan, Yu,Yao, Hui-Yu,et al. Interleukin-3 promotes hemangioblast development in mouse aorta-gonad-mesonephros region[J]. HAEMATOLOGICA-THE HEMATOLOGY JOURNAL,2010,95(6):875-883.
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