文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
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
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
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 @ 2025

Lgr6 表达的功能性指甲干样细胞来源于人诱导多能干细胞。

Lgr6-expressing functional nail stem-like cells differentiated from human-induced pluripotent stem cells.

机构信息

Innovative Regenerative Medicine, Graduate School of Medicine, Kansai Medical University, Hirakata city, Osaka, Japan.

Osaka College of High-Technology, Osaka City, Osaka, Japan.

出版信息

PLoS One. 2024 May 14;19(5):e0303260. doi: 10.1371/journal.pone.0303260. eCollection 2024.


DOI:10.1371/journal.pone.0303260
PMID:38743670
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11093308/
Abstract

The nail matrix containing stem cell populations produces nails and may contribute to fingertip regeneration. Nails are important tissues that maintain the functions of the hand and foot for handling objects and locomotion. Tumor chemotherapy impairs nail growth and, in many cases, loses them, although not permanently. In this report, we have achieved the successful differentiation of nail stem (NS)-like cells from human-induced pluripotent stem cells (iPSCs) via digit organoids by stepwise stimulation, tracing the molecular processes involved in limb development. Comprehensive mRNA sequencing analysis revealed that the digit organoid global gene expression profile fits human finger development. The NS-like cells expressed Lgr6 mRNA and protein and produced type-I keratin, KRT17, and type-II keratin, KRT81, which are abundant in nails. Furthermore, we succeeded in producing functional Lgr6-reporter human iPSCs. The reporter iPSC-derived Lgr6-positive cells also produced KRT17 and KRT81 proteins in the percutaneously transplanted region. To the best of our knowledge, this is the first report of NS-like cell differentiation from human iPSCs. Our differentiation method and reporter construct enable the discovery of drugs for nail repair and possibly fingertip-regenerative therapy.

摘要

甲母质包含干细胞群体,产生指甲并可能有助于指尖再生。指甲是维持手和脚功能的重要组织,用于处理物体和运动。肿瘤化疗会损害指甲生长,并在许多情况下导致指甲丢失,尽管不是永久性的。在本报告中,我们通过逐步刺激指状类器官成功地从人诱导多能干细胞(iPSC)中分化出指甲干(NS)样细胞,追踪了涉及肢体发育的分子过程。全面的 mRNA 测序分析表明,类器官的全局基因表达谱与人类手指发育相吻合。NS 样细胞表达 Lgr6 mRNA 和蛋白,并产生大量存在于指甲中的 I 型角蛋白 KRT17 和 II 型角蛋白 KRT81。此外,我们成功地产生了功能性 Lgr6 报告基因 iPSC。在经皮移植区域,报告基因 iPSC 衍生的 Lgr6 阳性细胞也产生了 KRT17 和 KRT81 蛋白。据我们所知,这是首例从人 iPSC 中分化出 NS 样细胞的报告。我们的分化方法和报告基因构建体使发现指甲修复和指尖再生治疗药物成为可能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75cb/11093308/0a4602a59a45/pone.0303260.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75cb/11093308/781d4d3ce4f0/pone.0303260.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75cb/11093308/1ad13a9ab538/pone.0303260.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75cb/11093308/76a0c115fc4c/pone.0303260.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75cb/11093308/0a4602a59a45/pone.0303260.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75cb/11093308/781d4d3ce4f0/pone.0303260.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75cb/11093308/1ad13a9ab538/pone.0303260.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75cb/11093308/76a0c115fc4c/pone.0303260.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75cb/11093308/0a4602a59a45/pone.0303260.g004.jpg

相似文献

[1]
Lgr6-expressing functional nail stem-like cells differentiated from human-induced pluripotent stem cells.

PLoS One. 2024

[2]
Lgr6 marks nail stem cells and is required for digit tip regeneration.

Proc Natl Acad Sci U S A. 2015-10-27

[3]
Human nail stem cells are retained but hypofunctional during aging.

J Mol Histol. 2018-4-9

[4]
Generation of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids.

J Hepatol. 2019-7-9

[5]
Self-assembly of differentiated progenitor cells facilitates spheroid human skin organoid formation and planar skin regeneration.

Theranostics. 2021

[6]
Paracrine signals regulate human liver organoid maturation from induced pluripotent stem cells.

Development. 2017-3-15

[7]
Identification and Isolation of Human LGR5+ Cells Using an Antibody-Based Strategy.

Methods Mol Biol. 2020

[8]
Are fingernails a key to unlocking the puzzle of mammalian limb regeneration?

Exp Dermatol. 2017-2-19

[9]
Differentiation of Human Induced Pluripotent Stem Cells to Mammary-like Organoids.

Stem Cell Reports. 2017-2-14

[10]
Human Cytomegalovirus Compromises Development of Cerebral Organoids.

J Virol. 2019-8-13

引用本文的文献

[1]
Reporter Alleles in hiPSCs: Visual Cues on Development and Disease.

Int J Mol Sci. 2024-10-13

本文引用的文献

[1]
Development of cartilage tissue using a stirred bioreactor and human iPSC-derived limb bud mesenchymal cells.

Biochem Biophys Res Commun. 2023-12-20

[2]
SRplot: A free online platform for data visualization and graphing.

PLoS One. 2023

[3]
En1 and Lmx1b do not recapitulate embryonic dorsal-ventral limb patterning functions during mouse digit tip regeneration.

Cell Rep. 2022-11-22

[4]
Identification of marker genes to monitor residual iPSCs in iPSC-derived products.

Cytotherapy. 2023-1

[5]
Wnt Signaling Coordinates the Expression of Limb Patterning Genes During Axolotl Forelimb Development and Regeneration.

Front Cell Dev Biol. 2022-4-21

[6]
Sox9 Is Required for Nail-Bed Differentiation and Digit-Tip Regeneration.

J Invest Dermatol. 2022-10

[7]
Comparative Analysis of Type I Keratin Expression By Nail Consistency: An Immunohistochemistry Study.

Appl Immunohistochem Mol Morphol. 2022-4-1

[8]
A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case report.

BMC Med Genomics. 2021-11-1

[9]
Apical ectodermal ridge regulates three principal axes of the developing limb.

J Zhejiang Univ Sci B.

[10]
LGRs in Skeletal Tissues: An Emerging Role for Wnt-Associated Adult Stem Cell Markers in Bone.

JBMR Plus. 2020-7-3

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索