• 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

从人类胚胎干细胞高效体外生成功能性胸腺上皮祖细胞。

Efficient in vitro generation of functional thymic epithelial progenitors from human embryonic stem cells.

作者信息

Su Min, Hu Rong, Jin Jingjun, Yan Yuan, Song Yinhong, Sullivan Ryan, Lai Laijun

机构信息

1] Department of Allied Health Sciences, University of Connecticut, Storrs, CT [2] Guiyang Medical College, Guizhou, China.

Department of Allied Health Sciences, University of Connecticut, Storrs, CT.

出版信息

Sci Rep. 2015 Jun 5;5:9882. doi: 10.1038/srep09882.

DOI:10.1038/srep09882
PMID:26044259
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4456731/
Abstract

Thymic epithelial cells (TECs) are the major components of the thymic microenvironment for T cell development. TECs are derived from thymic epithelial progenitors (TEPs). It has been reported that human ESCs (hESCs) can be directed to differentiate into TEPs in vitro. However, the efficiency for the differentiation is low. Furthermore, transplantation of hESC-TEPs in mice only resulted in a very low level of human T cell development from co-transplanted human hematopoietic precursors. We show here that we have developed a novel protocol to efficiently induce the differentiation of hESCs into TEPs in vitro. When transplanted into mice, hESC-TEPs develop into TECs and form a thymic architecture. Most importantly, the hESC-TECs support the long-term development of functional mouse T cells or a higher level of human T cell development from co-transplanted human hematopoietic precursors. The hESC-TEPs may provide a new approach to prevent or treat patients with T cell immunodeficiency.

摘要

胸腺上皮细胞(TECs)是T细胞发育的胸腺微环境的主要组成部分。TECs来源于胸腺上皮祖细胞(TEPs)。据报道,人类胚胎干细胞(hESCs)可在体外被诱导分化为TEPs。然而,分化效率较低。此外,将hESC-TEPs移植到小鼠体内,与共移植的人类造血前体细胞共同培养时,仅导致非常低水平的人类T细胞发育。我们在此表明,我们已经开发出一种新方案,可在体外高效诱导hESCs分化为TEPs。当移植到小鼠体内时,hESC-TEPs可发育为TECs并形成胸腺结构。最重要的是,hESC-TECs支持功能性小鼠T细胞的长期发育,或支持共移植的人类造血前体细胞实现更高水平的人类T细胞发育。hESC-TEPs可能为预防或治疗T细胞免疫缺陷患者提供一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f2/4456731/32b99fa89979/srep09882-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f2/4456731/226aa092e4a2/srep09882-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f2/4456731/94e3b53a824c/srep09882-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f2/4456731/d2eb622e5b72/srep09882-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f2/4456731/d0f1dd82aa7f/srep09882-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f2/4456731/32b99fa89979/srep09882-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f2/4456731/226aa092e4a2/srep09882-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f2/4456731/94e3b53a824c/srep09882-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f2/4456731/d2eb622e5b72/srep09882-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f2/4456731/d0f1dd82aa7f/srep09882-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f2/4456731/32b99fa89979/srep09882-f5.jpg

相似文献

1
Efficient in vitro generation of functional thymic epithelial progenitors from human embryonic stem cells.从人类胚胎干细胞高效体外生成功能性胸腺上皮祖细胞。
Sci Rep. 2015 Jun 5;5:9882. doi: 10.1038/srep09882.
2
Generation of thymic epithelial cell progenitors by mouse embryonic stem cells.利用小鼠胚胎干细胞生成胸腺上皮细胞祖细胞。
Stem Cells. 2009 Dec;27(12):3012-20. doi: 10.1002/stem.238.
3
Transplantation of Donor-Origin Mouse Embryonic Stem Cell-Derived Thymic Epithelial Progenitors Prevents the Development of Chronic Graft-versus-Host Disease in Mice.供体来源的小鼠胚胎干细胞衍生的胸腺上皮祖细胞移植可预防小鼠慢性移植物抗宿主病的发生。
Stem Cells Transl Med. 2017 Jan;6(1):121-130. doi: 10.5966/sctm.2016-0012. Epub 2016 Aug 2.
4
Directed differentiation of human embryonic stem cells into thymic epithelial progenitor-like cells reconstitutes the thymic microenvironment in vivo.人胚胎干细胞的定向分化为胸腺上皮祖细胞样细胞,在体内重建了胸腺微环境。
Cell Stem Cell. 2013 Aug 1;13(2):230-6. doi: 10.1016/j.stem.2013.06.014.
5
Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development.从人类胚胎干细胞生成功能性胸腺上皮细胞,支持宿主 T 细胞发育。
Cell Stem Cell. 2013 Aug 1;13(2):219-29. doi: 10.1016/j.stem.2013.04.004. Epub 2013 May 16.
6
Administration of embryonic stem cell-derived thymic epithelial progenitors expressing MOG induces antigen-specific tolerance and ameliorates experimental autoimmune encephalomyelitis.表达 MOGE 的胚胎干细胞源性胸腺上皮祖细胞的给药可诱导抗原特异性耐受并改善实验性自身免疫性脑脊髓炎。
J Autoimmun. 2015 Apr;58:36-47. doi: 10.1016/j.jaut.2015.01.002. Epub 2015 Jan 22.
7
Thymic Epithelial Cells Induced from Pluripotent Stem Cells by a Three-Dimensional Spheroid Culture System Regenerates Functional T Cells in Nude Mice.通过三维球体培养系统从多能干细胞诱导产生的胸腺上皮细胞在裸鼠体内再生功能性T细胞。
Cell Reprogram. 2015 Oct;17(5):368-75. doi: 10.1089/cell.2015.0006. Epub 2015 Sep 8.
8
Generation of functional human thymic cells from induced pluripotent stem cells.诱导多能干细胞生成功能性人胸腺细胞。
J Allergy Clin Immunol. 2022 Feb;149(2):767-781.e6. doi: 10.1016/j.jaci.2021.07.021. Epub 2021 Jul 29.
9
Mouse embryonic stem cell-derived thymic epithelial cell progenitors enhance T-cell reconstitution after allogeneic bone marrow transplantation.鼠胚胎干细胞衍生的胸腺上皮细胞祖细胞增强异基因骨髓移植后的 T 细胞重建。
Blood. 2011 Sep 22;118(12):3410-8. doi: 10.1182/blood-2011-03-340794. Epub 2011 Jul 26.
10
Administration of Amyloid Precursor Protein Gene Deleted Mouse ESC-Derived Thymic Epithelial Progenitors Attenuates Alzheimer's Pathology.淀粉样前体蛋白基因敲除小鼠 ESC 衍生的胸腺上皮祖细胞的给药可减轻阿尔茨海默病病理。
Front Immunol. 2020 Aug 11;11:1781. doi: 10.3389/fimmu.2020.01781. eCollection 2020.

引用本文的文献

1
An iPSC-based in vitro model recapitulates human thymic epithelial development and multi-lineage specification.一种基于诱导多能干细胞的体外模型概括了人类胸腺上皮发育和多谱系分化。
Nat Commun. 2025 Aug 25;16(1):7680. doi: 10.1038/s41467-025-62523-1.
2
Endogenous thymic regeneration: restoring T cell production following injury.内源性胸腺再生:损伤后恢复T细胞生成
Nat Rev Immunol. 2025 Jan 6. doi: 10.1038/s41577-024-01119-0.
3
Transcriptional and epigenetic characterization of a new in vitro platform to model the formation of human pharyngeal endoderm.

本文引用的文献

1
FOXN1 (GFP/w) reporter hESCs enable identification of integrin-β4, HLA-DR, and EpCAM as markers of human PSC-derived FOXN1(+) thymic epithelial progenitors.FOXN1 (GFP/w) 报告基因 hESC 可鉴定整合素-β4、HLA-DR 和 EpCAM 为人类 PSC 来源的 FOXN1(+) 胸腺上皮前体细胞的标志物。
Stem Cell Reports. 2014 May 22;2(6):925-37. doi: 10.1016/j.stemcr.2014.04.009. eCollection 2014 Jun 3.
2
Tbx1 modulates endodermal and mesodermal differentiation from mouse induced pluripotent stem cells.Tbx1 调节小鼠诱导多能干细胞的内胚层和中胚层分化。
Stem Cells Dev. 2014 Jul 1;23(13):1491-500. doi: 10.1089/scd.2013.0488. Epub 2014 Apr 2.
3
转录组学和表观遗传学表征人类咽内胚层形成的新型体外模型平台。
Genome Biol. 2024 Aug 8;25(1):211. doi: 10.1186/s13059-024-03354-z.
4
Generation and molecular characterization of human pluripotent stem cell-derived pharyngeal foregut endoderm.人多能干细胞源性咽前肠内胚层的生成与分子特征。
Dev Cell. 2023 Sep 25;58(18):1801-1818.e15. doi: 10.1016/j.devcel.2023.08.024.
5
The beta cell-immune cell interface in type 1 diabetes (T1D).1 型糖尿病中胰岛β细胞与免疫细胞的相互作用。
Mol Metab. 2023 Dec;78:101809. doi: 10.1016/j.molmet.2023.101809. Epub 2023 Sep 20.
6
Engineering CpG island DNA methylation in pluripotent cells through synthetic CpG-free ssDNA insertion.通过合成不含 CpG 的 ssDNA 插入来实现多能干细胞中的 CpG 岛 DNA 甲基化工程化。
Cell Rep Methods. 2023 May 4;3(5):100465. doi: 10.1016/j.crmeth.2023.100465. eCollection 2023 May 22.
7
Human thymus in health and disease: Recent advances in diagnosis and biology.健康与疾病中的人类胸腺:诊断和生物学的最新进展。
Semin Immunol. 2023 Mar;66:101732. doi: 10.1016/j.smim.2023.101732. Epub 2023 Feb 28.
8
Differentiation of Pluripotent Stem Cells Into Thymic Epithelial Cells and Generation of Thymic Organoids: Applications for Therapeutic Strategies Against APECED.多能干细胞向胸腺上皮细胞的分化及胸腺类器官的生成:针对自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良治疗策略的应用
Front Immunol. 2022 Jun 29;13:930963. doi: 10.3389/fimmu.2022.930963. eCollection 2022.
9
Modeling human T1D-associated autoimmune processes.模拟人类 T1D 相关的自身免疫过程。
Mol Metab. 2022 Feb;56:101417. doi: 10.1016/j.molmet.2021.101417. Epub 2021 Dec 10.
10
Human stem cell-derived thymic epithelial cells enhance human T-cell development in a xenogeneic thymus.人源干细胞衍生的胸腺上皮细胞在异种胸腺中增强人 T 细胞发育。
J Allergy Clin Immunol. 2022 May;149(5):1755-1771. doi: 10.1016/j.jaci.2021.09.038. Epub 2021 Oct 22.
FOXN1 in organ development and human diseases.
叉头框蛋白N1在器官发育和人类疾病中的作用
Int Rev Immunol. 2014 Mar;33(2):83-93. doi: 10.3109/08830185.2013.870171. Epub 2014 Jan 17.
4
Recombinant IL-7/HGFβ hybrid cytokine enhances T cell recovery in mice following allogeneic bone marrow transplantation.重组白细胞介素-7/肝细胞生长因子β杂交细胞因子可增强异基因骨髓移植后小鼠的T细胞恢复。
PLoS One. 2013 Dec 12;8(12):e82998. doi: 10.1371/journal.pone.0082998. eCollection 2013.
5
Human proT-cells generated in vitro facilitate hematopoietic stem cell-derived T-lymphopoiesis in vivo and restore thymic architecture.体外生成的人 proT 细胞有助于体内造血干细胞衍生的 T 淋巴细胞生成,并恢复胸腺结构。
Blood. 2013 Dec 19;122(26):4210-9. doi: 10.1182/blood-2012-12-472803. Epub 2013 Nov 8.
6
Directed differentiation of human embryonic stem cells into thymic epithelial progenitor-like cells reconstitutes the thymic microenvironment in vivo.人胚胎干细胞的定向分化为胸腺上皮祖细胞样细胞,在体内重建了胸腺微环境。
Cell Stem Cell. 2013 Aug 1;13(2):230-6. doi: 10.1016/j.stem.2013.06.014.
7
Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development.从人类胚胎干细胞生成功能性胸腺上皮细胞,支持宿主 T 细胞发育。
Cell Stem Cell. 2013 Aug 1;13(2):219-29. doi: 10.1016/j.stem.2013.04.004. Epub 2013 May 16.
8
Insights on FoxN1 biological significance and usages of the "nude" mouse in studies of T-lymphopoiesis.对 FoxN1 生物学意义的深入了解以及“裸鼠”在 T 淋巴细胞生成研究中的应用。
Int J Biol Sci. 2012;8(8):1156-67. doi: 10.7150/ijbs.5033. Epub 2012 Sep 24.
9
Mechanisms of thymus organogenesis and morphogenesis.胸腺发生和形态发生的机制。
Development. 2011 Sep;138(18):3865-78. doi: 10.1242/dev.059998.
10
Mouse embryonic stem cell-derived thymic epithelial cell progenitors enhance T-cell reconstitution after allogeneic bone marrow transplantation.鼠胚胎干细胞衍生的胸腺上皮细胞祖细胞增强异基因骨髓移植后的 T 细胞重建。
Blood. 2011 Sep 22;118(12):3410-8. doi: 10.1182/blood-2011-03-340794. Epub 2011 Jul 26.