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动态响应光的RhoA活性调节3D矩阵中的机械敏感干细胞命运决定

Jieung Baek¹, Sanjay Kumar², David V Schaffer³

¹Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Division of Mechanical and Biomedical Engineering, Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, 03760, Republic of Korea.

Biomaterials advances

|April 10, 2024

概括

时间机械线索调节神经干细胞 (NSC) 的命运. 脉冲RhoA激活在刚性3D矩阵上调调节Egr1,而静态激活影响Egr1跨硬度,影响神经发生.

科学领域:

生物医学工程生物医学工程
干细胞生物学干细胞生物学
机械生物学机械生物学

背景情况:

干细胞的行为受到其利基中的动态机械线索的影响.
了解这些动态如何影响干细胞谱系在3D中的承诺至关重要.
早期生长反应1基因 (Egr1) 是神经干细胞 (NSC) 机械敏感系的3D矩阵特异调解者.

研究的目的:

调查如何暂时变化的机械信号调节3D中的EGR1表达.
阐明RhoA信号动态在机械转导和干细胞命运中的作用.
为了确定矩阵刚度对RhoA介导的Egr1调节的影响.

主要方法:

利用基于Arabidopsis thaliana加密-2的光激活系统暂时控制RhoA活动.
在静态和脉冲RhoA激活下,研究了不同硬度的3D凝中的Egr1表达.
评估了在RhoA介导的EGR1上调中actin组合的作用.
研究了静态与脉冲RhoA激活对软3D凝中神经发生的作用.

主要成果:

脉冲RhoA激活在刚性3D凝中专门调节了Egr1.
静态光刺激增加了Egr1在3D凝硬度的广泛范围内的表达.
在RhoA激活后,抑制动因组合会损害Egr1上调.
静态RhoA激活,与脉冲激活不同,限制了软凝中的神经发生.

结论:

在3D矩阵中,RhoA激活的动态极大地影响了Egr1介导的干细胞命运.
这种影响取决于3D微环境的机械特性,特别是刚性.
对于Egr1上调和随后的干细胞命运决定,RhoA信号需要依赖于actin的过程.

关键词:

早期生长反应 (Egr1)机械感应感应机械感应神经干细胞 (NSC) 是一种神经干细胞.视觉遗传学视觉遗传学拉斯同类家族成员A (RhoA) 信号传导.

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