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Circulation:SOX17调节人成纤维细胞向内皮细胞和红细胞转化

2017-04-09 MedSci MedSci原创

成人成纤维细胞转变为功能性内皮细胞这一去分化和谱系转化的机制尚未完全明确。此外,成纤维细胞去分化为内皮细胞和造血细胞谱系是否模拟重现胚胎发育过程中的多能祖细胞产生尚未可知。近期美国学者发表题为《SOX17通过分化成CD34 +祖细胞调节人成纤维细胞向内皮细胞和红细胞的转化》的研究文章于著名血管杂志Circulation,该研究发现发育转录因子SOX17通过产生介导性祖细胞调节成纤维细胞的双系转化作

成人成纤维细胞转变为功能性内皮细胞这一去分化和谱系转化的机制尚未完全明确。此外,成纤维细胞去分化为内皮细胞和造血细胞谱系是否模拟重现胚胎发育过程中的多能祖细胞产生尚未可知。

近期美国学者发表题为《SOX17通过分化成CD34 +祖细胞调节人成纤维细胞向内皮细胞和红细胞的转化》的研究文章于著名血管杂志Circulation,该研究发现发育转录因子SOX17通过产生介导性祖细胞调节成纤维细胞的双系转化作用。

诱导性内皮细胞iECs表达特异性内皮细胞表面标志物,也表现出细胞增殖和新生血管形成的能力。诱导性红细胞表达红细胞表面标志物并形成红系菌落。内皮谱系转化依赖于发育转录因子SOX17的上调,而抑制SOX17反而将其导向为红细胞。将这些人CD34 +祖细胞植入免疫缺陷型NOD-SCID小鼠导致人内皮细胞介导的微血管形成,管内由小鼠和人类红细胞充斥。人成纤维细胞产生的iECs表现出端粒酶上调。细胞移植显着改善心肌梗死后的血管分布和心脏功能,而无任何畸胎瘤形成迹象。

成纤维细胞向介导性CD34 +祖细胞分化,并以SOX17依赖性方式产生内皮细胞和红细胞。这一发现将介导性CD34 +祖细胞状态作为识别的关键分叉点,通过调节其产生功能性血管或红细胞挽救缺血组织。

原始出处: Zhang L,Jambusaria A,et al. SOX17 Regulates Conversion of Human Fibroblasts into Endothelial Cells and Erythroblasts via De-Differentiation into CD34+ Progenitor Cells. Circulation. 2017 Apr 5. pii: CIRCULATIONAHA.116.025722.

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