• 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

Myc 依赖性 Gata6 表皮细胞去分化类似于终末分化的逆转。

Myc-dependent dedifferentiation of Gata6 epidermal cells resembles reversal of terminal differentiation.

机构信息

Centre for Gene Therapy and Regenerative Medicine, King's College London, London, UK.

Department of Physics, Randall Centre for Cell and Molecular Biophysics, Centre for the Physical Science of Life and London Centre for Nanotechnology, King's College London, London, UK.

出版信息

Nat Cell Biol. 2023 Oct;25(10):1426-1438. doi: 10.1038/s41556-023-01234-5. Epub 2023 Sep 21.

DOI:10.1038/s41556-023-01234-5
PMID:37735598
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10567550/
Abstract

Dedifferentiation is the process by which terminally differentiated cells acquire the properties of stem cells. During mouse skin wound healing, the differentiated Gata6-lineage positive cells of the sebaceous duct are able to dedifferentiate. Here we have integrated lineage tracing and single-cell mRNA sequencing to uncover the underlying mechanism. Gata6-lineage positive and negative epidermal stem cells in wounds are transcriptionally indistinguishable. Furthermore, in contrast to reprogramming of induced pluripotent stem cells, the same genes are expressed in the epidermal dedifferentiation and differentiation trajectories, indicating that dedifferentiation does not involve adoption of a new cell state. We demonstrate that dedifferentiation is not only induced by wounding, but also by retinoic acid treatment or mechanical expansion of the epidermis. In all three cases, dedifferentiation is dependent on the master transcription factor c-Myc. Mechanotransduction and actin-cytoskeleton remodelling are key features of dedifferentiation. Our study elucidates the molecular basis of epidermal dedifferentiation, which may be generally applicable to adult tissues.

摘要

去分化是终末分化细胞获得干细胞特性的过程。在小鼠皮肤伤口愈合过程中，皮脂腺导管中分化的 Gata6 谱系阳性细胞能够去分化。在这里，我们整合了谱系追踪和单细胞 mRNA 测序，以揭示潜在的机制。伤口中 Gata6 谱系阳性和阴性的表皮干细胞在转录上无法区分。此外，与诱导多能干细胞的重编程相反，在表皮去分化和分化轨迹中表达相同的基因，表明去分化不涉及采用新的细胞状态。我们证明，去分化不仅由创伤诱导，还可由维甲酸处理或表皮机械扩张诱导。在所有三种情况下，去分化都依赖于主转录因子 c-Myc。机械转导和肌动蛋白细胞骨架重塑是去分化的关键特征。我们的研究阐明了表皮去分化的分子基础，这可能普遍适用于成人组织。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/2a4a6fb57b6f/41556_2023_1234_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/37f096eceab2/41556_2023_1234_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/54fa5040ddcf/41556_2023_1234_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/b044b269d18f/41556_2023_1234_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/dcf4075a1959/41556_2023_1234_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/4212683e693f/41556_2023_1234_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/2985fc362729/41556_2023_1234_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/530bcc1d3277/41556_2023_1234_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/043ae266cfbf/41556_2023_1234_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/5333c4bec87a/41556_2023_1234_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/fc6e573ad85f/41556_2023_1234_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/f0be929e8004/41556_2023_1234_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/9314ca9b04ea/41556_2023_1234_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/2a4a6fb57b6f/41556_2023_1234_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/37f096eceab2/41556_2023_1234_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/54fa5040ddcf/41556_2023_1234_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/b044b269d18f/41556_2023_1234_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/dcf4075a1959/41556_2023_1234_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/4212683e693f/41556_2023_1234_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/2985fc362729/41556_2023_1234_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/530bcc1d3277/41556_2023_1234_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/043ae266cfbf/41556_2023_1234_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/5333c4bec87a/41556_2023_1234_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/fc6e573ad85f/41556_2023_1234_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/f0be929e8004/41556_2023_1234_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/9314ca9b04ea/41556_2023_1234_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2716/10567550/2a4a6fb57b6f/41556_2023_1234_Fig13_ESM.jpg

相似文献

1
Myc-dependent dedifferentiation of Gata6 epidermal cells resembles reversal of terminal differentiation.Myc 依赖性 Gata6 表皮细胞去分化类似于终末分化的逆转。
Nat Cell Biol. 2023 Oct;25(10):1426-1438. doi: 10.1038/s41556-023-01234-5. Epub 2023 Sep 21.
2
Wounding induces dedifferentiation of epidermal Gata6 cells and acquisition of stem cell properties.创伤诱导表皮Gata6细胞去分化并获得干细胞特性。
Nat Cell Biol. 2017 Jun;19(6):603-613. doi: 10.1038/ncb3532. Epub 2017 May 15.
3
Dedifferentiation derived cells exhibit phenotypic and functional characteristics of epidermal stem cells.去分化衍生细胞表现出表皮干细胞的表型和功能特征。
J Cell Mol Med. 2010 May;14(5):1135-45. doi: 10.1111/j.1582-4934.2009.00765.x.
4
Wnt/β-catenin signaling is critical for dedifferentiation of aged epidermal cells in vivo and in vitro.Wnt/β-catenin 信号通路对于体内和体外衰老表皮细胞的去分化至关重要。
Aging Cell. 2012 Feb;11(1):14-23. doi: 10.1111/j.1474-9726.2011.00753.x. Epub 2011 Oct 31.
5
Emergence and properties of adult mammalian epidermal stem cells.成年哺乳动物表皮干细胞的出现和特性。
Dev Biol. 2024 Nov;515:129-138. doi: 10.1016/j.ydbio.2024.07.014. Epub 2024 Jul 24.
6
[Effects of skin γδ T lymphocytes on wound healing of mice through regulating proliferation and differentiation of mice epidermal cells].[皮肤γδ T淋巴细胞通过调控小鼠表皮细胞增殖与分化对小鼠伤口愈合的影响]
Zhonghua Shao Shang Za Zhi. 2019 Apr 20;35(4):298-307. doi: 10.3760/cma.j.issn.1009-2587.2019.04.010.
7
Nicotine promotes initiation and progression of KRAS-induced pancreatic cancer via Gata6-dependent dedifferentiation of acinar cells in mice.尼古丁通过 Gata6 依赖性去分化胰腺腺泡细胞促进 KRAS 诱导的胰腺癌的发生和进展。
Gastroenterology. 2014 Nov;147(5):1119-33.e4. doi: 10.1053/j.gastro.2014.08.002. Epub 2014 Aug 12.
8
Characterization of bipotential epidermal progenitors derived from human sebaceous gland: contrasting roles of c-Myc and beta-catenin.源自人皮脂腺的双能表皮祖细胞的特性：c-Myc和β-连环蛋白的不同作用
Stem Cells. 2008 May;26(5):1241-52. doi: 10.1634/stemcells.2007-0651. Epub 2008 Feb 28.
9
c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny.转基因小鼠表皮中的c-Myc激活导致干细胞动员及其子代分化。
Curr Biol. 2001 Apr 17;11(8):558-68. doi: 10.1016/s0960-9822(01)00154-3.
10
Reprogramming primordial germ cells into pluripotent stem cells.将原始生殖细胞重编程为多能干细胞。
PLoS One. 2008;3(10):e3531. doi: 10.1371/journal.pone.0003531. Epub 2008 Oct 27.

引用本文的文献

1
Muscle fiber Myc is dispensable for muscle growth and its forced expression severely perturbs homeostasis.肌纤维Myc对于肌肉生长并非必需，其强制表达会严重扰乱体内平衡。
Nat Commun. 2025 Apr 3;16(1):3190. doi: 10.1038/s41467-025-58542-7.
2
Caspase-8-dependent autophagy regulates neutrophil infiltration in oral squamous cell carcinoma.半胱天冬酶8依赖性自噬调节口腔鳞状细胞癌中的中性粒细胞浸润。
Proc Natl Acad Sci U S A. 2024 Dec 10;121(50):e2406944121. doi: 10.1073/pnas.2406944121. Epub 2024 Dec 3.
3
Molecular profiles, sources and lineage restrictions of stem cells in an annelid regeneration model.

本文引用的文献

1
CellRank for directed single-cell fate mapping.细胞排序用于有向单细胞命运图谱绘制。
Nat Methods. 2022 Feb;19(2):159-170. doi: 10.1038/s41592-021-01346-6. Epub 2022 Jan 13.
2
A FIJI macro for quantifying pattern in extracellular matrix.斐济宏指令：用于量化细胞外基质中模式的方法。
Life Sci Alliance. 2021 Jan 27;4(3). doi: 10.26508/lsa.202000880. Print 2021 Mar.
3
Mechanical Stiffness Controls Dendritic Cell Metabolism and Function.机械刚度控制树突状细胞代谢和功能。
环节动物再生模型中干细胞的分子特征、来源和谱系限制。
Nat Commun. 2024 Nov 18;15(1):9882. doi: 10.1038/s41467-024-54041-3.
4
Manipulating Myc for reparative regeneration.操控Myc以实现修复性再生。
Front Cell Dev Biol. 2024 Mar 21;12:1357589. doi: 10.3389/fcell.2024.1357589. eCollection 2024.
Cell Rep. 2021 Jan 12;34(2):108609. doi: 10.1016/j.celrep.2020.108609.
4
Tuning the Chern number in quantum anomalous Hall insulators.在量子反常霍尔绝缘体中调谐陈数。
Nature. 2020 Dec;588(7838):419-423. doi: 10.1038/s41586-020-3020-3. Epub 2020 Dec 16.
5
Durotaxis: The Hard Path from In Vitro to In Vivo.杜罗塔克斯：从体外到体内的艰难之路。
Dev Cell. 2021 Jan 25;56(2):227-239. doi: 10.1016/j.devcel.2020.11.019. Epub 2020 Dec 7.
6
Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis.GATA6 对人类上毛囊皮脂腺单位稳态和痤疮发病机制的贡献。
Nat Commun. 2020 Oct 20;11(1):5067. doi: 10.1038/s41467-020-18784-z.
7
Mechanics of a multilayer epithelium instruct tumour architecture and function.多层上皮的力学特性可指导肿瘤的结构和功能。
Nature. 2020 Sep;585(7825):433-439. doi: 10.1038/s41586-020-2695-9. Epub 2020 Sep 2.
8
Mechanisms of stretch-mediated skin expansion at single-cell resolution.单细胞分辨率下拉伸介导的皮肤扩张机制。
Nature. 2020 Aug;584(7820):268-273. doi: 10.1038/s41586-020-2555-7. Epub 2020 Jul 29.
9
Disease-associated keratin mutations reduce traction forces and compromise adhesion and collective migration.疾病相关的角蛋白突变会降低牵引力，损害细胞黏附和集体迁移。
J Cell Sci. 2020 Jul 29;133(14):jcs243956. doi: 10.1242/jcs.243956.
10
Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage.异染色质驱动的核软化可保护基因组免受机械应激诱导的损伤。
Cell. 2020 May 14;181(4):800-817.e22. doi: 10.1016/j.cell.2020.03.052. Epub 2020 Apr 16.