<br>MgFe-LDH 通过不同细胞膜受体的时间选择性激活对 ESC 细胞命运的双向调节,Advanced Functional Materials

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MgFe-LDH 通过不同细胞膜受体的时间选择性激活对 ESC 细胞命运的双向调节
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2024-04-12 , DOI: 10.1002/adfm.202314112
Zhaojie Wang _{1,

2} , Yuxin Bai _{1,

2} , Xu Xu ₁ , Yanjing Zhu ₁ , Xiaolie He ₁ , Ruiqi Huang ₁ , Liqun Yu ₁ , Runzhi Huang ₁ , Liming Cheng ₁ , Rongrong Zhu _{1,

2}

Affiliation

生物材料对干细胞命运的调控具有相当大的治疗潜力；然而，生物材料指导干细胞进行准确命运调控的机制仍需阐明。层状双氢氧化物（LDH）纳米颗粒因其优异的理化性质和生物相容性而广泛用于组织再生。本研究揭示MgFe-LDH对小鼠胚胎干细胞向神经祖细胞的分化具有双向调节作用，本质上抑制第1天细胞分化，促进第3天细胞分化。单细胞转录组测序和结构分析模拟计算表明，MgFe-LDH 与膜受体白血病抑制因子受体（LIFR，细胞膜上方 15 nm）和 pached1（PTCH1，细胞膜上方 6 nm）一号相互作用和分化的第3天，分别。 LIFR 与 MgFe-LDH 的接触比 PTCH1 更多，且静电相互作用能相对较弱（PTCH1 和 LIFR 分别为 -11010.0 和 -9829.3 kJ mol ^-1 ）。这些因素决定了受体结合和激活的优先顺序，然后是细胞命运的调节。研究结果表明，MgFe-LDH对干细胞的活性和命运具有双重调节作用，从而通过对细胞膜受体的深入研究，为神经发育和再生医学的个性化治疗创造了可能性。

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Two-Way Regulation of MgFe-LDH on ESC Cell Fate via Temporal Selective Activation of Different Cell Membrane Receptors

Stem cell fate regulation by biomaterials has considerable therapeutic potential; however, the mechanisms whereby biomaterials instruct stem cells for accurate fate regulation still need to be elucidated. Layered double hydroxide (LDH) nanoparticles are widely used for tissue regeneration because of their excellent physicochemical properties and biocompatibility. This study reveals that MgFe-LDH has bidirectional regulatory effects on the differentiation of mouse embryonic stem cells into neural progenitor cells, essentially suppressing cell differentiation on the 1st day and promoting cell differentiation on the 3rd day. Single-cell transcriptome sequencing and simulated computation of structural analysis demonstrate that MgFe-LDH interacts with the membrane receptors leukemia inhibitory factor receptor (LIFR, 15 nm above the cell membrane) and pached1 (PTCH1, 6 nm above the cell membrane) on the 1st and 3rd day of differentiation, respectively. LIFR has more contact with MgFe-LDH than PTCH1 and relatively weaker electrostatic interaction energies (−11010.0 and −9829.3 kJ mol⁻¹ for PTCH1 and LIFR, respectively). These factors determine receptor binding and activation priority, followed by cell fate regulation. The results indicate that MgFe-LDH regulate the activity and fate of stem cells dually, thus creating possibilities for personalized therapy in neurodevelopment and regenerative medicine through an in-depth study of cell membrane receptors.

更新日期：2024-04-12

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