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表达ABCG2的克隆再生内皮细胞有助于形成和维持血管

Yang Lin^1,2,3, Chang-Hyun Gil^2,4, Kimihiko Banno^2,5

¹Division of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine (Y. Lin, M. Yokoyama, Y. Liu, M.S., M.G., K.C., F.G., J.M.G.S., R.S., D.R., S.R.), Weill Cornell Medicine, New York, NY.

|April 29, 2024

概括

研究人员在人类和小鼠中确定了表达ATP结合盒子子子家族G成员2 (ABCG2) 的内皮细胞 (ECs) 作为血管克隆重组细胞 (CRECs). 这些ABCEC可以再生血管,为血管修复提供新的细胞疗法.

科学领域:

血管生物学
干细胞生物学
复原医学

背景情况:

大多数器官依赖于长期存活的干细胞/原生细胞.
成熟的内皮细胞 (ECs) 的再生潜力有限,血管干细胞/原生细胞的存在尚不清楚.
缺少血管克隆重组EC (CREC) 的特定标志物,阻碍了对其自我更新和血管形成机制的研究.

研究的目的:

识别和表征具有EC重组潜力的血管干细胞/原始细胞.
确定表达ABCG2的EC是否在人类和小鼠血管中充当CREC.
阐明这些细胞的再生潜力的分子机制.

主要方法:

分析人类血管中的ABCG2表达EC的殖民地形成,自我更新和血管形成潜力.
在发育期间和心肌梗塞损伤后,开发Abcg2Cre^Ert2;ROSA TdTomato小鼠的血统追踪.
用RNA测序和ChIP测序来研究表达Abcg2的EC中的基因调节.

主要成果:

具有较高ABCG2表达 (ABCECs) 的内皮细胞在人体和小鼠血管中表现出增强的克隆增殖和体内血管形成潜力.
移植研究证实了ABCECs对受体血管形成的克隆作用.
血统追踪表明,表达Abcg2的CRECs (AbcCRECs) 在心肌梗塞后促进动脉,静脉和毛细血管的发育和再生.
转录组和表观遗传分析显示,ABCREC中的血管生成和血管发育基因特征得到了丰富,像Notch2和Hey2这样的特定血管生成基因显示出双价性组织蛋白修饰.

结论:

这项研究确定了小鼠和人类血管CREC的前性标志物 (ABCG2表达).
这些发现确定了ABCEC作为具有显著再生能力的CREC的功能性身份.
鉴定CREC及其调节机制有望开发用于血管修复的新细胞疗法,例如内皮功能障碍.

关键词:

血管新生血管血管发育生物学内皮细胞

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