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在潜在的血源性内皮和内心脏中,Scl抑制心肌形成
Ben Van Handel1, Amélie Montel-Hagen, Rajkumar Sasidharan
1Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell
|August 7, 2012
概括
转录因子Scl/Tal1对于将内皮细胞指定为血液干细胞而不是心脏细胞至关重要. 它的缺失导致胚胎内皮形成意想不到的心脏组织,揭示了内皮可塑性.
科学领域:
- 发育生物学是发展生物学.
- 干细胞生物学 干细胞生物学
- 心血管研究的心血管研究.
背景情况:
- 胚胎内皮形成了造血干细胞和祖细胞.
- 确定内皮细胞命运的精确机制仍然不清楚.
研究的目的:
- 研究转录因子Scl/Tal1在确定内皮细胞命运中的作用.
- 了解Scl/Tal1如何防止内皮细胞对心脏血统的错误规范.
主要方法:
- 对Scl/Tal1淘汰赛 (Scl-/-) 胚胎的分析.
- 对血源性内皮和黄囊内皮的研究.
- 使用Scl (fl/fl) Rosa26Cre-ER (T2) 胚胎进行Scl的马赛克删除.
- 基因表达分析,包括Wnt对抗剂.
主要成果:
- 缺少Scl/Tal1导致胚胎内皮中心脏转录程序的激活.
- 在Scl-/-胚胎中观察到异位心脏发生,其中内皮细胞分化为心肌细胞.
- 对Scl/Tal1的细胞内在和时间要求,以防止内皮的心肌生成.
- 在Scl-/-内皮中Wnt抗体的升调促进了异位心肌细胞的分化.
结论:
- Scl/Tal1对于建立造血程序和预防血源性内皮内皮中的心肌生成至关重要.
- 胚胎内皮表现出显著的可塑性,Scl/Tal1损失诱导子宫外心形成.
- 这项研究揭示了Scl/Tal1在维持内皮细胞身份和预防血统不忠方面发挥的新角色.
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