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原信号传递和矩阵刚度调节了小鼠腺上皮干细胞中的多能性
Chen Jiang1, Alessia Centonze1, Yura Song1
1Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Nature communications
|December 18, 2024
概括
原I和细胞外矩阵刚性可以恢复成年基底干细胞 (BaSCs) 腺上皮的多能性. 这一发现突出了干细胞可塑性的关键信号通路.
科学领域:
- 干细胞生物学 干细胞生物学
- 细胞外矩阵动态 细胞外矩阵动态
- 腺体上皮质的发展.
背景情况:
- 腺体上皮质,像乳腺和前列腺一样,由光线和基底细胞组成.
- 成人基底干细胞 (BaSCs) 通常表现出单能分化,但在特定条件下可以恢复多能.
- 控制BASC多功率再激活的机制在很大程度上是未知的.
研究的目的:
- 调查成年基底干细胞中多能性重新激活的分子机制.
- 确定关键的细胞外基质组件和干细胞可塑性所涉及的信号通路.
主要方法:
- 在各种多能诱导条件下,分析基底干细胞中的原I表达.
- 利用乳腺和前列腺器官模型来评估细胞外基质 (ECM) 刚度和原度的影响.
- 在硬的ECM条件下培养的乳腺器官上进行单细胞RNA测序 (scRNA-seq).
主要成果:
- 原I表达在经过多功率再诱导的基底干细胞中被持续上调.
- 增加的原度和ECM刚度在有机体模型中促进了基底干细胞多能性.
- 在硬的ECM环境中,β1整合素/FAK/AP-1信号轴对于调节基底干细胞多能性至关重要.
结论:
- 原I信号传递和细胞外矩阵刚性是成年基底干细胞多能性在腺上皮质中的关键调节者.
- 这项研究揭示了一种涉及干细胞可塑性的ECM介导控制的新机制,这对再生医学和癌症研究具有影响.
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