Effects of Univariate Stiffness and Degradation of DNA Hydrogels on the Transcriptomics of Neural Progenitor Cells,Journal of the American Chemical Society

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Effects of Univariate Stiffness and Degradation of DNA Hydrogels on the Transcriptomics of Neural Progenitor Cells
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2023-04-08 , DOI: 10.1021/jacs.2c13373
Bini Zhou ₁ , Bo Yang _{1,

2} , Qian Liu ₃ , Lu Jin _{3,

4} , Yu Shao ₁ , Taoyang Yuan _{4,

5} , Ya-Nan Zhang ₆ , Chao Wang ₁ , Ziwei Shi ₇ , Xin Li ₁ , Yufan Pan ₁ , Ning Qiao _{3,

4} , Jiang-Fei Xu ₈ , Yuhe Renee Yang ₉ , Yuanchen Dong ₇ , Lijin Xu ₆ , Songbai Gui ₄ , Dongsheng Liu ₁

Affiliation

Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
Sinopec Beijing Research Institute of Chemical Industry, Beijing 100013, China.
Beijing Neurosurgical Institute, Capital Medical University, Beijing 100071, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China.
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Department of Chemistry, Renmin University of China, Beijing 100872, China.
CAS Key Laboratory of Colloid Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100190, China.
Key Laboratory of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084, China.
CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

Mechanical interactions between cells and extracellular matrix (ECM) are critical for stem cell fate decision. Synthetic models of ECM, such as hydrogels, can be used to precisely manipulate the mechanical properties of the cell niche and investigate how mechanical signals regulate the cell behavior. However, it has long been a great challenge to tune solely the ECM-mimic hydrogels’ mechanical signals since altering the mechanical properties of most materials is usually accompanied by chemical and topological changes. Here, we employ DNA and its enantiomers to prepare a series of hydrogels with univariate stiffness regulation, which enables a precise interpretation of the fate decision of neural progenitor cells (NPCs) in a three-dimensional environment. Using single-cell RNA sequencing techniques, Monocle pseudotime trajectory and CellphoneDB analysis, we demonstrate that the stiffness of the hydrogel alone does not influence the differentiation of NPCs, but the degradation of the hydrogel that enhances cell–cell interactions is possibly the main reason. We also find that ECM remodeling facilitates cells to sense mechanical stimuli.

中文翻译：

DNA 水凝胶的单变量刚度和降解对神经祖细胞转录组学的影响

细胞和细胞外基质 (ECM) 之间的机械相互作用对于干细胞命运决定至关重要。ECM 的合成模型，如水凝胶，可用于精确操纵细胞生态位的机械特性，并研究机械信号如何调节细胞行为。然而，长期以来，仅调整 ECM 模拟水凝胶的机械信号一直是一个巨大的挑战，因为改变大多数材料的机械性能通常伴随着化学和拓扑变化。在这里，我们使用 DNA 及其对映体制备了一系列具有单变量刚度调节的水凝胶，这使得能够精确解释神经祖细胞 (NPC) 在三维环境中的命运决定。使用单细胞RNA测序技术，Monocle pseudotime 轨迹和 CellphoneDB 分析，我们证明水凝胶的刚度本身不会影响 NPC 的分化，但增强细胞间相互作用的水凝胶的降解可能是主要原因。我们还发现 ECM 重塑有助于细胞感知机械刺激。

更新日期：2023-04-08

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