PDF(Pubmed)
Abstract：
UNASSIGNED: The committed differentiation fate regulation has been a difficult problem in the fields of stem cell research, evidence showed that nanomaterials could promote the differentiation of stem cells into specific cell types. Layered double hydroxide (LDH) nanoparticles possess the regulation function of stem cell fate, while the underlying mechanism needs to be investigated. In this study, the process of embryonic stem cells (ESCs) differentiate to neural progenitor cells (NPCs) by magnesium aluminum LDH (MgAl-LDH) was investigated.
UNASSIGNED: MgAl-LDH with diameters of 30, 50, and 100 nm were synthesized and characterized, and their effects on the cytotoxicity and differentiation of NPCs were detected in vitro. Dot blot and MeRIP-qPCR were performed to detect the level of m6A RNA methylation in nanoparticles-treated cells.
UNASSIGNED: Our work displayed that LDH nanoparticles of three different sizes were biocompatible with NPCs, and the addition of MgAl-LDH could significantly promote the process of ESCs differentiate to NPCs. 100 nm LDH has a stronger effect on promoting NPCs differentiation compared to 30 nm and 50 nm LDH. In addition, dot blot results indicated that the enhanced NPCs differentiation by MgAl-LDH was closely related to m6A RNA methylation process, and the major modification enzyme in LDH controlled NPCs differentiation may be the m6A RNA methyltransferase METTL3. The upregulated METTL3 by LDH increased the m6A level of Sox1 mRNA, enhancing its stability.
UNASSIGNED: This work reveals that MgAl-LDH nanoparticles can regulate the differentiation of ESCs into NPCs by increasing m6A RNA methylation modification of Sox1.
UNASSIGNED: MgAl-LDH with diameters of 30, 50, and 100 nm were synthesized and characterized, and their effects on the cytotoxicity and differentiation of NPCs were detected in vitro. Dot blot and MeRIP-qPCR were performed to detect the level of m6A RNA methylation in nanoparticles-treated cells.
UNASSIGNED: Our work displayed that LDH nanoparticles of three different sizes were biocompatible with NPCs, and the addition of MgAl-LDH could significantly promote the process of ESCs differentiate to NPCs. 100 nm LDH has a stronger effect on promoting NPCs differentiation compared to 30 nm and 50 nm LDH. In addition, dot blot results indicated that the enhanced NPCs differentiation by MgAl-LDH was closely related to m6A RNA methylation process, and the major modification enzyme in LDH controlled NPCs differentiation may be the m6A RNA methyltransferase METTL3. The upregulated METTL3 by LDH increased the m6A level of Sox1 mRNA, enhancing its stability.
UNASSIGNED: This work reveals that MgAl-LDH nanoparticles can regulate the differentiation of ESCs into NPCs by increasing m6A RNA methylation modification of Sox1.
摘要：
■分化命运调控一直是干细胞研究领域的难题，证据表明，纳米材料可以促进干细胞分化为特定的细胞类型。层状双氢氧化物(LDH)纳米粒子具有调节干细胞命运的功能,而潜在的机制需要研究。在这项研究中,研究了镁铝LDH（MgAl-LDH）诱导胚胎干细胞（ESCs）向神经祖细胞（NPCs）分化的过程。
■合成并表征了直径为30、50和100nm的MgAl-LDH，并在体外检测了它们对NPCs细胞毒性和分化的影响。进行点印迹和MeRIP-qPCR以检测纳米颗粒处理的细胞中m6ARNA甲基化的水平。
■我们的工作表明，三种不同大小的LDH纳米颗粒与NPC具有生物相容性，MgAl-LDH的添加能显著促进ESCs向NPCs分化。与30nm和50nm的LDH相比，100nm的LDH具有更强的促进NPCs分化的作用。此外,斑点印迹结果表明,MgAl-LDH增强NPCs分化与m6ARNA甲基化过程密切相关,LDH控制的NPCs分化中的主要修饰酶可能是m6ARNA甲基转移酶METTL3。LDH上调的METTL3增加了Sox1mRNA的m6A水平，增强其稳定性。
■这项工作揭示了MgAl-LDH纳米颗粒可以通过增加Sox1的m6ARNA甲基化修饰来调节ESC向NPC的分化。
■合成并表征了直径为30、50和100nm的MgAl-LDH，并在体外检测了它们对NPCs细胞毒性和分化的影响。进行点印迹和MeRIP-qPCR以检测纳米颗粒处理的细胞中m6ARNA甲基化的水平。
■我们的工作表明，三种不同大小的LDH纳米颗粒与NPC具有生物相容性，MgAl-LDH的添加能显著促进ESCs向NPCs分化。与30nm和50nm的LDH相比，100nm的LDH具有更强的促进NPCs分化的作用。此外,斑点印迹结果表明,MgAl-LDH增强NPCs分化与m6ARNA甲基化过程密切相关,LDH控制的NPCs分化中的主要修饰酶可能是m6ARNA甲基转移酶METTL3。LDH上调的METTL3增加了Sox1mRNA的m6A水平，增强其稳定性。
■这项工作揭示了MgAl-LDH纳米颗粒可以通过增加Sox1的m6ARNA甲基化修饰来调节ESC向NPC的分化。
