间充质干细胞
刚度
转录组
调节器
细胞生物学
生物
基因表达
计算生物学
材料科学
基因
遗传学
复合材料
作者
Max Darnell,Luo Gu,David J. Mooney
出处
期刊:Biomaterials
[Elsevier]
日期:2018-10-01
卷期号:181: 182-188
被引量:63
标识
DOI:10.1016/j.biomaterials.2018.07.039
摘要
Substrate stiffness has been recognized as an important regulator of cell fate and function, but an understanding of the full extent of processes affected by stiffness is lacking as its transcriptome-wide effects have not been mapped. This limited understanding has restricted the contexts in which engineers can employ stiffness as an engineering design parameter. To address these limitations, we performed RNA-seq on mesenchymal stem cells (MSCs) cultured in alginate hydrogels over a range of moduli to broadly map the transcriptome-wide changes associated with stiffness sensing. We found a large number of stiffness-sensitive genes, and that many genes respond to stiffness in nonlinear ways. Informed by these differential expression results, we explored a hypothesis related to current MSC clinical activity, and found that stiffness can regulate the expression of MSC immunomodulatory markers in response to cytokine stimulation. Overall, these results reveal previously unknown features of MSC stiffness response and demonstrate the value of coupling –omics approaches with biophysical experiments.
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