奇拉性诱导的基因系强制执行机械敏感的介质细胞干细胞跨越细菌层边界
Ankita Das1, Shreya Adhikary1, Amit Roy Chowdhury1,2
1Centre for Healthcare Science and Technology, Indian Institute of Engineering Science and Technology, Shibpur, India.
Stem cell reviews and reports
|November 16, 2023
概括
矩阵刚度会影响介质干细胞的命运,促进上皮细胞过渡 (MET). 较硬的基板可通过机器学习验证,对表皮细胞标记物进行上调和对介质细胞标记物进行下调. 这一发现有助于组织工程应用.
科学领域:
- 生物材料科学 生物材料科学
- 干细胞生物学 干细胞生物学
- 再生医学是一种再生医学.
背景情况:
- 中细胞到上皮细胞的过渡 (MET) 对于发育和修复至关重要,而上皮细胞到中细胞的过渡 (EMT) 与癌症有关.
- 微环境调制,特别是矩阵刚度,可以影响细胞信号传输并诱导EMT/MET,但其在促进MET中的作用较少被探索.
- 了解矩阵刚性如何影响干细胞命运对于组织再生和器官生成的应用至关重要.
研究的目的:
- 调查矩阵刚度对诱导带衍生中介细胞干细胞 (UCMSC) 中MET的影响.
- 探索微环境诱导的不对称细胞分裂在推动MET中的作用.
- 建立基质刚度,机械传导通路和MET之间的相关性.
主要方法:
- UCMSC是在多甲基酸盐 (PDMS) 基质上培养的,硬度各不相同.
- 分析了机械传导,极性,细胞命运决定因素,上皮,炎症和介质细胞标记物的表达.
- 细胞周期分析,转录学研究和机器学习模型被用来验证发现.
主要成果:
- 更硬的PDMS矩阵显著上调机械传导,极性和上皮标记物,同时降低UCMSC中的炎症和介质细胞标记物.
- 转录组分析证实在更硬的基底上表皮标记基因的表达更高,EMT标记基因的表达更低.
- 一个机器学习模型在将矩阵刚度与MET相关联时获得了94%的准确性,并开发了一个评分系统来分类混合上皮质/介质细胞状态.
结论:
- 基质刚度是指导UCMSC向表皮表型 (MET) 的关键因素.
- YAP/TAZ机械传导通路,EMT信号传递和不对称的细胞分裂都参与了硬度依赖的MET.
- 这项研究为利用具有特定刚性的生物工程基质为组织工程和再生医学中控制干细胞分化提供了基础.
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