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利用遗传谱系示踪技术探究小鼠胚胎期多器官静脉内皮的动脉命运转归

Zheng Xin-Yan Ding Xiao-Chen Hou Si-Yuan Jiang Mei-Lin Liu Bing Lan Yu

解放军医学杂志2025,Vol.50Issue(12):1540-1548,9.
解放军医学杂志2025,Vol.50Issue(12):1540-1548,9.DOI:10.11855/j.issn.0577-7402.1611.2025.1120

利用遗传谱系示踪技术探究小鼠胚胎期多器官静脉内皮的动脉命运转归

Genetic lineage tracing reveals arterial fate conversion of venous endothelia in multiple organs during mouse embryogenesis

Zheng Xin-Yan 1Ding Xiao-Chen 2Hou Si-Yuan 2Jiang Mei-Lin 1Liu Bing 3Lan Yu4

作者信息

  • 1. Key Laboratory for Regenerative Medicine of Ministry of Education,Institute of Hematology,School of Medicine,Jinan University,Guangzhou,Guangdong 510632,China
  • 2. Medical Innovation Research Division,Chinese PLA General Hospital,Beijing 100853,China
  • 3. Institute of Hematology,Department of Hematology,Fifth Medical Center,Chinese PLA General Hospital/Haihe Laboratory of Cell Ecosystem/State Key Laboratory of Experimental Hematology,Beijing 100071,China
  • 4. Key Laboratory for Regenerative Medicine of Ministry of Education,Institute of Hematology,School of Medicine,Jinan University,Guangzhou,Guangdong 510632,China||Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College/Haihe Laboratory of Cell Ecosystem/State Key Laboratory of Experimental Hematology,Tianjin 300020,China
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摘要

Abstract

Objective To investigate the temporal window of venous-to-arterial conversion and the long-term fate of embryonic venous-derived arterial endothelial cells during mid-to-late gestation,in neonates,and in adulthood through genetic lineage tracing.Methods Using the Nr2f2-CrexER;Gja5-EGFP;Rosa-H2b-mcherry genetic lineage tracing mouse model,tamoxifen induction was performed at embryonic days E9.5 and E11.5.Tissues(spleen,thymus,adrenal gland)were collected at E15.5,E18.5,neonatal stage(postnatal day 7),and adult stage(8-week-old)for immunofluorescence staining and flow cytometry to assess venous lineage contribution to arterial endothelial cells and fate conversion.Results Tamoxifen induction at E9.5 revealed that venous endothelia persistently contributed to arterial endothelial cells in the spleen,thymus,and adrenal gland into adulthood,indicating the long-term persistence of embryonic venous-derived arterial endothelial cells within the vascular network.At E13.5,Nr2f2 expression still showed a pattern mutually exclusive with the arterial marker gene Gja5,thus displaying venous endothelial characteristics.The venous lineage was able to contribute to the arterial endothelial cells of the spleen,thymus,and adrenal gland when induced at E11.5,indicating that venous-to-arterial conversion events still occurred at E11.5.Conclusion The time window for venous-to-arterial conversion spans from E9.5 to E11.5 in mouse embryos.Embryonic venous endothelia can make a long-term contribution to the arterial endothelial cells of the spleen,thymus,and adrenal gland.

关键词

血管内皮细胞/动脉生成/遗传谱系示踪/静脉-动脉转化/胚胎发育

Key words

vascular endothelial cells/arteriogenesis/genetic lineage tracing/venous-to-arterial fate conversion/embryonic development

分类

医药卫生

引用本文复制引用

Zheng Xin-Yan,Ding Xiao-Chen,Hou Si-Yuan,Jiang Mei-Lin,Liu Bing,Lan Yu..利用遗传谱系示踪技术探究小鼠胚胎期多器官静脉内皮的动脉命运转归[J].解放军医学杂志,2025,50(12):1540-1548,9.

基金项目

This work was supported by the National Key Research and Development Program of China(2022YFA1103501) 国家重点研发计划(2022YFA1103501) (2022YFA1103501)

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