• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

受损的炎症环境会颠覆多能干细胞衍生的人类神经干细胞中由 TET2 形成的表观遗传景观。

Injured inflammatory environment overrides the TET2 shaped epigenetic landscape of pluripotent stem cell derived human neural stem cells.

机构信息

Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, 92697-1705, USA.

Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, 92697-4475, USA.

出版信息

Sci Rep. 2024 Oct 24;14(1):25186. doi: 10.1038/s41598-024-75689-3.

DOI:10.1038/s41598-024-75689-3
PMID:39448736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11502794/
Abstract

Spinal cord injury creates an inflammatory microenvironment that regulates the capacity of transplanted human Neural Stem Cells (hNSC) to migrate, differentiate, and repair injury. Despite similarities in gene expression and markers detected by immunostaining, hNSC populations exhibit heterogeneous therapeutic potential. This heterogeneity derives in part from the epigenetic landscape in the hNSC genome, specifically methylation (5mC) and hydroxymethylation (5hmC) state, which may affect the response of transplanted hNSC in the injury microenvironment and thereby modulate repair capacity. We demonstrate a significant up-regulation of methylcytosine dioxygenase 2 gene (TET2) expression in undifferentiated hNSC derived from human embryonic stem cells (hES-NSC), and report that this is associated with hES-NSC competence for differentiation marker expression. TET2 protein catalyzes active demethylation and TET2 upregulation could be a signature of pluripotent exit, while shaping the epigenetic landscape in hES-NSC. We determine that the inflammatory environment overrides epigenetic programming in vitro and in vivo by directly modulating TET2 expression levels in hES-NSC to change cell fate. We also report the effect of cell fate and microenvironment on differential methylation 5mC/5hmC balance. Understanding how the activity of epigenetic modifiers changes within the transplantation niche in vivo is crucial for assessment of hES-NSC behavior for potential clinical applications.

摘要

脊髓损伤会产生一个炎症微环境，调节移植的人神经干细胞（hNSC）的迁移、分化和修复损伤的能力。尽管 hNSC 群体在基因表达和免疫染色检测到的标记物上存在相似性，但它们表现出异质性的治疗潜力。这种异质性部分源于 hNSC 基因组中的表观遗传景观，特别是甲基化（5mC）和羟甲基化（5hmC）状态，这可能会影响移植 hNSC 在损伤微环境中的反应，从而调节修复能力。我们证明了未分化的人胚胎干细胞（hES-NSC）来源的 hNSC 中，二氧嘧啶酶 2 基因（TET2）的表达显著上调，并报告说这与 hES-NSC 分化标志物表达的能力有关。TET2 蛋白催化活性去甲基化，TET2 的上调可能是多能性退出的标志，同时塑造 hES-NSC 的表观遗传景观。我们确定炎症环境通过直接调节 hES-NSC 中的 TET2 表达水平，在体外和体内改变细胞命运，从而超越了表观遗传编程。我们还报告了细胞命运和微环境对差异甲基化 5mC/5hmC 平衡的影响。了解表观遗传修饰剂在体内移植龛内的活性如何变化，对于评估 hES-NSC 的行为及其在潜在临床应用中的潜力至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/1d41787f06aa/41598_2024_75689_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/902f0d057d83/41598_2024_75689_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/d0a0c9a23aed/41598_2024_75689_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/96a1e97e1506/41598_2024_75689_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/c8ee45d531d0/41598_2024_75689_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/647c70c35d79/41598_2024_75689_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/c0ad57ef678d/41598_2024_75689_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/126d9ff16e3b/41598_2024_75689_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/1d41787f06aa/41598_2024_75689_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/902f0d057d83/41598_2024_75689_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/d0a0c9a23aed/41598_2024_75689_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/96a1e97e1506/41598_2024_75689_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/c8ee45d531d0/41598_2024_75689_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/647c70c35d79/41598_2024_75689_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/c0ad57ef678d/41598_2024_75689_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/126d9ff16e3b/41598_2024_75689_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf9/11502794/1d41787f06aa/41598_2024_75689_Fig8_HTML.jpg

相似文献

1
Injured inflammatory environment overrides the TET2 shaped epigenetic landscape of pluripotent stem cell derived human neural stem cells.受损的炎症环境会颠覆多能干细胞衍生的人类神经干细胞中由 TET2 形成的表观遗传景观。
Sci Rep. 2024 Oct 24;14(1):25186. doi: 10.1038/s41598-024-75689-3.
2
DNA methylcytosine dioxygenase ten-eleven translocation 2 enhances lipopolysaccharide-induced cytokine expression in human dental pulp cells by regulating MyD88 hydroxymethylation.TET2 通过调控 MyD88 的羟甲基化增强脂多糖诱导的人牙髓细胞细胞因子表达。
Cell Tissue Res. 2018 Aug;373(2):477-485. doi: 10.1007/s00441-018-2826-x. Epub 2018 Apr 13.
3
Dynamic switching of active promoter and enhancer domains regulates Tet1 and Tet2 expression during cell state transitions between pluripotency and differentiation.在多能性和分化之间的细胞状态转变过程中，活性启动子和增强子结构域的动态切换调节Tet1和Tet2的表达。
Mol Cell Biol. 2015 Mar;35(6):1026-42. doi: 10.1128/MCB.01172-14. Epub 2015 Jan 12.
4
TET2 regulates extranodal NK/T cell lymphoma progression through regulation of DNA methylation.TET2 通过调控 DNA 甲基化调控结外 NK/T 细胞淋巴瘤的进展。
Hematol Oncol. 2024 Jul;42(4):e3295. doi: 10.1002/hon.3295.
5
Association of high 5-hydroxymethylcytosine levels with Ten Eleven Translocation 2 overexpression and inflammation in Sjögren's syndrome patients.高 5-羟甲基胞嘧啶水平与 Sjögren 综合征患者 11 号染色体转位 2 过表达和炎症的相关性。
Clin Immunol. 2018 Nov;196:85-96. doi: 10.1016/j.clim.2018.06.002. Epub 2018 Jun 9.
6
Epigenetic Regulation of Corneal Epithelial Differentiation by TET2.TET2 通过表观遗传调控角膜上皮细胞分化。
Int J Mol Sci. 2023 Feb 2;24(3):2841. doi: 10.3390/ijms24032841.
7
Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation.小鼠胚胎干细胞及其分化过程中 5-羟甲基胞嘧啶的动态调控
Nature. 2011 May 19;473(7347):398-402. doi: 10.1038/nature10008. Epub 2011 Apr 3.
8
Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development.Tet1 和 Tet2 联合缺失导致表观遗传异常，但与出生后发育相容。
Dev Cell. 2013 Feb 11;24(3):310-23. doi: 10.1016/j.devcel.2012.12.015. Epub 2013 Jan 24.
9
Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2.体细胞重编程早期阶段的组蛋白修饰酶 Parp1 和 Tet2 作用
Nature. 2012 Aug 30;488(7413):652-5. doi: 10.1038/nature11333.
10
TET2 coactivates gene expression through demethylation of enhancers.TET2 通过去甲基化增强子来激活基因表达。
Sci Adv. 2018 Nov 7;4(11):eaau6986. doi: 10.1126/sciadv.aau6986. eCollection 2018 Nov.

本文引用的文献

1
Zinc finger proteins: insights into the transcriptional and post transcriptional regulation of immune response.锌指蛋白：对免疫反应的转录和转录后调控的深入了解。
Mol Biol Rep. 2021 Jul;48(7):5735-5743. doi: 10.1007/s11033-021-06556-x. Epub 2021 Jul 24.
2
TET Enzymes and 5-Hydroxymethylcytosine in Neural Progenitor Cell Biology and Neurodevelopment.TET 酶与 5-羟甲基胞嘧啶在神经祖细胞生物学和神经发育中的作用
Front Cell Dev Biol. 2021 Feb 18;9:645335. doi: 10.3389/fcell.2021.645335. eCollection 2021.
3
Role of CD133 in human embryonic stem cell proliferation and teratoma formation.
CD133 在人胚胎干细胞增殖和畸胎瘤形成中的作用。
Stem Cell Res Ther. 2020 May 27;11(1):208. doi: 10.1186/s13287-020-01729-0.
4
Controlling properties of human neural progenitor cells using 2D and 3D conductive polymer scaffolds.使用 2D 和 3D 导电聚合物支架控制人神经祖细胞的特性。
Sci Rep. 2019 Dec 20;9(1):19565. doi: 10.1038/s41598-019-56021-w.
5
Metascape provides a biologist-oriented resource for the analysis of systems-level datasets.Metascape 为系统水平数据集的分析提供了面向生物学家的资源。
Nat Commun. 2019 Apr 3;10(1):1523. doi: 10.1038/s41467-019-09234-6.
6
Intra-individual methylomics detects the impact of early-life adversity.个体内甲基组学检测到早期生活逆境的影响。
Life Sci Alliance. 2019 Apr 1;2(2). doi: 10.26508/lsa.201800204. Print 2019 Apr.
7
Neuroinflammation in the central nervous system: Symphony of glial cells.中枢神经系统中的神经炎症：神经胶质细胞的交响曲。
Glia. 2019 Jun;67(6):1017-1035. doi: 10.1002/glia.23571. Epub 2018 Dec 11.
8
Decoding the role of TET family dioxygenases in lineage specification.解析 TET 家族双加氧酶在谱系特化中的作用。
Epigenetics Chromatin. 2018 Oct 5;11(1):58. doi: 10.1186/s13072-018-0228-7.
9
Dynamic DNA methylation: In the right place at the right time.动态 DNA 甲基化：在适当的时间出现在适当的位置。
Science. 2018 Sep 28;361(6409):1336-1340. doi: 10.1126/science.aat6806.
10
The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury.中枢神经系统的细胞外环境：对脊髓损伤后可塑性、发芽和轴突再生的影响。
Neural Plast. 2018 Apr 18;2018:2952386. doi: 10.1155/2018/2952386. eCollection 2018.