RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Photoactivatable Materials for Versatile Single-Cell Patterning Based on the Photocaging of Cell-Anchoring Moieties through Lipid Self-Assembly.
Photoactivatable Materials for Versatile Single-Cell Patterning Based on the Photocaging of Cell-Anchoring Moieties through Lipid Self-Assembly.
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在单细胞分辨率下对多种类型细胞进行图案化的通用方法已成为细胞分析、基于细胞的器件构建和组织工程中日益重要的技术。在此,我们提出了一种基于聚乙二醇(PEG)-脂质的光活化材料,用于对多种细胞进行图案化,而不论其黏附能力如何。
在本研究中,首先证明带有双脂肪酸链的PEG-脂质能够完全抑制细胞在其涂层基底表面上的锚定,而单链脂质则通过脂质-细胞膜相互作用稳定地锚定细胞。基于这一发现,合成了一种同时具有一条正常脂肪酸链和一条可光裂解脂肪酸链的PEG-脂质,作为一种可通过光照将链数从两条转变为一条的材料。在可光转换的PEG-脂质表面上,细胞锚定通过光照被激活。高速原子力显微镜测量揭示,这种脂质-细胞膜相互作用的光笼蔽效应之所以发生,是因为疏水性双链自组装成纳米级结构并协同抑制锚定。光诱导的脂质组装体解离通过局部光激活锚定相互作用,实现了多种细胞的光引导精细图案化。利用该表面,人NK 细胞和白血病细胞可以被定位以逐一相互作用。随后通过显微镜监测单个免疫细胞的细胞毒性能力,展示了其在高通量分析单个细胞间通讯异质性中的应用原理验证。
因此,涂覆有我们的光活化材料的基底可以作为一个多功能平台,用于精确快速地图案化多元素细胞,以实现基于细胞间通讯的诊断。
Versatile methods for patterning multiple types of cells with single-cell resolution have become an increasingly important technology for cell analysis, cell-based device construction, and tissue engineering.
Here, we present a photoactivatable material based on poly(ethylene glycol) (PEG)-lipids for patterning a variety of cells, regardless of their adhesion abilities. In this study, PEG-lipids bearing dual fatty acid chains were first shown to perfectly suppress cell anchoring on their coated substrate surfaces whereas those with single-chain lipids stably anchored cells through lipid-cell membrane interactions. From this finding, a PEG-lipid with one each of both normal and photocleavable fatty acid chains was synthesized as a material that could convert the chain number from two to one by exposure to light. On the photoconvertible PEG-lipid surface, cell anchoring was activated by light exposure.
High-speed atomic force microscopy measurements revealed that this photocaging of the lipid-cell membrane interaction occurs because the hydrophobic dual chains self-assemble into nanoscale structures and cooperatively inhibit the anchoring. Light-induced dissociation of the lipid assembly achieved the light-guided fine patterning of multiple cells through local photoactivation of the anchoring interactions.
Using this surface, human natural killer cells and leukemia cells could be positioned to interact one-by-one. The cytotoxic capacity of single immune cells was then monitored via microscopy, showing the proof-of-principle for applications in the high-throughput analysis of the heterogeneity in individual cell-cell communications.
Thus, the substrate coated with our photoactivatable material can serve as a versatile platform for the accurate and rapid patterning of multiple-element cells for intercellular communication-based diagnostics.
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