Zfx控制胚胎和造血干细胞的自我更新
Jose M Galan-Caridad1, Sivan Harel, Teresita L Arenzana
1Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA.
Cell
|April 24, 2007
概括
转录因子Zfx是胚胎干细胞 (ESC) 和造血干细胞 (HSC) 的共同调节者. Zfx通过激活常见和特定的基因来控制两种细胞类型的自我更新.
科学领域:
- 干细胞生物学 干细胞生物学
- 分子遗传学 分子遗传学
- 转录法规 转录法规
背景情况:
- 干细胞 (SC) 具有自我更新能力,但控制多能胚胎SC (ESC) 和成人组织特异性SC (如造血性SC (HSC) 的机制尚不清楚.
- 了解共享的调节途径对于干细胞研究和治疗应用至关重要.
研究的目的:
- 调查是否有共同的机制来规范ESC和HSC的自我更新.
- 确定控制SC自我更新的共享转录调节器.
主要方法:
- 在小鼠ESC和HSC模型中利用基因删除和转录因子Zfx的过度表达.
- 分析了自我更新,分化,亡和基因表达特征.
- 在两种细胞类型中确定了Zfx的直接标基因.
主要成果:
- 删除Zfx损害了ESC自我更新,但没有影响分化;Zfx过度表达增强了ESC自我更新.
- Zfx删除取消了成年人HSC维护,但省略了胎儿HSC和祖先.
- 缺少Zfx的ESC和HSC呈现出增加的亡和与压力相关的基因表达.
- Zfx直接激活了ESC和HSC中常见的目标基因,以及ESC特定的基因,如Tbx3和Tcl1.
结论:
- 确定Zfx作为一个共享的转录调节器,对于ESC和HSC自我更新至关重要.
- 表明在胚胎和成人干细胞中自我更新的共同遗传基础.
- 强调Zfx在维持干细胞种群和反对分化方面的作用.
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