• 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

动态 MAPK/ERK 活性通过小生境调节维持肾祖细胞，并为分化前体细胞做好准备。

Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation.

机构信息

HiLIFE and Medicum, University of Helsinki, Helsinki FIN-00014, Finland.

Department of Pathology and Biology of Diseases, Graduate School of Medicine & Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.

出版信息

Stem Cell Reports. 2018 Oct 9;11(4):912-928. doi: 10.1016/j.stemcr.2018.08.012. Epub 2018 Sep 13.

DOI:10.1016/j.stemcr.2018.08.012
PMID:30220628
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6178244/
Abstract

The in vivo niche and basic cellular properties of nephron progenitors are poorly described. Here we studied the cellular organization and function of the MAPK/ERK pathway in nephron progenitors. Live-imaging of ERK activity by a Förster resonance energy transfer biosensor revealed a dynamic activation pattern in progenitors, whereas differentiating precursors exhibited sustained activity. Genetic experiments demonstrate that MAPK/ERK activity controls the thickness, coherence, and integrity of the nephron progenitor niche. Molecularly, MAPK/ERK activity regulates niche organization and communication with extracellular matrix through PAX2 and ITGA8, and is needed for CITED1 expression denoting undifferentiated status. MAPK/ERK activation in nephron precursors propels differentiation by priming cells for distal and proximal fates induced by the Wnt and Notch pathways. Thus, our results demonstrate a mechanism through which MAPK/ERK activity controls both progenitor maintenance and differentiation by regulating a distinct set of targets, which maintain the biomechanical milieu of tissue-residing progenitors and prime precursors for nephrogenesis.

摘要

肾祖细胞的体内生态位和基本细胞特性描述得很差。在这里，我们研究了肾祖细胞中 MAPK/ERK 通路的细胞组织和功能。通过Förster 共振能量转移生物传感器对 ERK 活性进行实时成像，揭示了祖细胞中存在动态激活模式，而分化前体细胞则表现出持续的活性。遗传实验表明，MAPK/ERK 活性控制着肾祖细胞生态位的厚度、连贯性和完整性。分子水平上，MAPK/ERK 活性通过 PAX2 和 ITGA8 调节生态位的组织和与细胞外基质的通讯，并且需要 CITED1 的表达来表示未分化状态。肾前体细胞中 MAPK/ERK 的激活通过启动细胞向 Wnt 和 Notch 途径诱导的远端和近端命运来推进分化。因此，我们的结果表明，MAPK/ERK 活性通过调节一组特定的靶标来控制祖细胞的维持和分化，这些靶标维持组织驻留祖细胞的生物力学环境，并为肾发生启动前体细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/fbaa3d839aaf/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/84914885bde6/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/2e9068dcb327/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/0c131796d282/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/0a8ea6f0dbc1/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/845b6861448b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/e9a326b8996e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/4e5de3a46be9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/fbaa3d839aaf/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/84914885bde6/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/2e9068dcb327/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/0c131796d282/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/0a8ea6f0dbc1/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/845b6861448b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/e9a326b8996e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/4e5de3a46be9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b4/6178244/fbaa3d839aaf/gr7.jpg

相似文献

1
Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation.动态 MAPK/ERK 活性通过小生境调节维持肾祖细胞，并为分化前体细胞做好准备。
Stem Cell Reports. 2018 Oct 9;11(4):912-928. doi: 10.1016/j.stemcr.2018.08.012. Epub 2018 Sep 13.
2
Mdm2 is required for maintenance of the nephrogenic niche.Mdm2 对于肾源龛的维持是必需的。
Dev Biol. 2014 Mar 1;387(1):1-14. doi: 10.1016/j.ydbio.2014.01.009. Epub 2014 Jan 17.
3
Omics profiling identifies the regulatory functions of the MAPK/ERK pathway in nephron progenitor metabolism.组学分析确定了 MAPK/ERK 通路在肾祖细胞代谢中的调节功能。
Development. 2022 Oct 1;149(19). doi: 10.1242/dev.200986. Epub 2022 Oct 3.
4
Repression of Interstitial Identity in Nephron Progenitor Cells by Pax2 Establishes the Nephron-Interstitium Boundary during Kidney Development.Pax2对肾单位祖细胞间质身份的抑制在肾脏发育过程中建立了肾单位-间质边界。
Dev Cell. 2017 May 22;41(4):349-365.e3. doi: 10.1016/j.devcel.2017.04.022.
5
p53 Enables metabolic fitness and self-renewal of nephron progenitor cells.p53 使肾祖细胞能够适应代谢并实现自我更新。
Development. 2015 Apr 1;142(7):1228-41. doi: 10.1242/dev.111617.
6
Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment.Wnt11 指导肾祖细胞的极性和运动行为，最终决定肾单位的数量。
Elife. 2018 Dec 5;7:e40392. doi: 10.7554/eLife.40392.
7
Notch signaling promotes nephrogenesis by downregulating Six2.Notch信号通路通过下调Six2来促进肾发生。
Development. 2016 Nov 1;143(21):3907-3913. doi: 10.1242/dev.143503. Epub 2016 Sep 15.
8
Comparative whole-genome transcriptome analysis in renal cell populations reveals high tissue specificity of MAPK/ERK targets in embryonic kidney.在肾细胞群体中的比较全基因组转录组分析表明 MAPK/ERK 靶点在胚胎肾中有很高的组织特异性。
BMC Biol. 2022 May 13;20(1):112. doi: 10.1186/s12915-022-01309-z.
9
Nephron progenitor commitment is a stochastic process influenced by cell migration.肾祖细胞的定向决定是一个受细胞迁移影响的随机过程。
Elife. 2019 Jan 24;8:e41156. doi: 10.7554/eLife.41156.
10
BMP7 promotes proliferation of nephron progenitor cells via a JNK-dependent mechanism.骨形态发生蛋白7通过一种依赖JNK的机制促进肾单位祖细胞的增殖。
Development. 2009 Nov;136(21):3557-66. doi: 10.1242/dev.036335. Epub 2009 Sep 30.

引用本文的文献

1
Integrin Alpha8 Beta1 (81): An In-Depth Review of an Overlooked RGD-Binding Receptor.整合素α8β1（81）：对一个被忽视的RGD结合受体的深入综述
Biocell. 2025;49(5):789-811. doi: 10.32604/biocell.2025.062325. Epub 2025 May 27.
2
Measurement of adhesion and traction of cells at high yield reveals an energetic ratchet operating during nephron condensation.高产量测量细胞的黏附和牵引力揭示了在肾单位浓缩过程中起作用的能量棘轮。
Proc Natl Acad Sci U S A. 2024 Sep 24;121(39):e2404586121. doi: 10.1073/pnas.2404586121. Epub 2024 Sep 18.
3
Mesangial cell-derived CircRNAs in chronic glomerulonephritis: RNA sequencing and bioinformatics analysis.

本文引用的文献

1
Cell adhesion and mechanics as drivers of tissue organization and differentiation: local cues for large scale organization.细胞黏附与力学特性作为组织与分化的驱动力：大规模组织的局部线索。
Curr Opin Cell Biol. 2018 Oct;54:89-97. doi: 10.1016/j.ceb.2018.05.003. Epub 2018 Jun 1.
2
Hamartin regulates cessation of mouse nephrogenesis independently of Mtor.错构瘤蛋白独立于 mTOR 调控鼠肾发生的停止。
Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):5998-6003. doi: 10.1073/pnas.1712955115. Epub 2018 May 21.
3
Haploinsufficiency for the Six2 gene increases nephron progenitor proliferation promoting branching and nephron number.
肾小球肾炎中系膜细胞衍生的 CircRNAs：RNA 测序和生物信息学分析。
Ren Fail. 2024 Dec;46(2):2371059. doi: 10.1080/0886022X.2024.2371059. Epub 2024 Jul 1.
4
Developmental and tissue-specific roles of mammalian centrosomes.哺乳动物中心体的发育及组织特异性作用
FEBS J. 2025 Feb;292(4):709-726. doi: 10.1111/febs.17212. Epub 2024 Jun 27.
5
The extracellular matrix protein fibronectin promotes metanephric kidney development.细胞外基质蛋白纤连蛋白促进后肾原基的发育。
Pflugers Arch. 2024 Jun;476(6):963-974. doi: 10.1007/s00424-024-02954-9. Epub 2024 Apr 2.
6
Measurement of adhesion and traction of cells at high yield (MATCHY) reveals an energetic ratchet driving nephron condensation.高产细胞黏附与牵引力测量法（MATCHY）揭示了一种驱动肾单位凝聚的能量棘轮机制。
bioRxiv. 2024 Feb 8:2024.02.07.579368. doi: 10.1101/2024.02.07.579368.
7
Glial cell line-derived neurotrophic factor and its role in attenuating renal fibrosis: a review.胶质细胞源性神经营养因子及其在减轻肾纤维化中的作用：综述
Korean J Intern Med. 2025 Mar;40(2):219-229. doi: 10.3904/kjim.2023.246. Epub 2023 Dec 13.
8
Nephron progenitors rhythmically alternate between renewal and differentiation phases that synchronize with kidney branching morphogenesis.肾单位祖细胞在与肾脏分支形态发生同步的更新和分化阶段之间有节奏地交替。
bioRxiv. 2024 Jan 13:2023.11.21.568157. doi: 10.1101/2023.11.21.568157.
9
Aberrant centrosome biogenesis disrupts nephron and collecting duct progenitor growth and fate resulting in fibrocystic kidney disease.异常的中心体生物发生破坏了肾单位和集合管祖细胞的生长和命运，导致纤维囊性肾病。
Development. 2023 Dec 15;150(24). doi: 10.1242/dev.201976. Epub 2023 Dec 21.
10
Independent control over cell patterning and adhesion on hydrogel substrates for tissue interface mechanobiology.用于组织界面机械生物学的水凝胶基质上细胞图案化和粘附的独立控制。
iScience. 2023 Apr 11;26(5):106657. doi: 10.1016/j.isci.2023.106657. eCollection 2023 May 19.
Six2 基因部分缺失会增加肾祖细胞的增殖，促进分支和肾单位数量。
Kidney Int. 2018 Mar;93(3):589-598. doi: 10.1016/j.kint.2017.09.015. Epub 2017 Dec 6.
4
A Strong Contractile Actin Fence and Large Adhesions Direct Human Pluripotent Colony Morphology and Adhesion.强收缩肌动蛋白栅栏和大黏附物指导人类多能性集落形态和黏附。
Stem Cell Reports. 2017 Jul 11;9(1):67-76. doi: 10.1016/j.stemcr.2017.05.021. Epub 2017 Jun 15.
5
Repression of Interstitial Identity in Nephron Progenitor Cells by Pax2 Establishes the Nephron-Interstitium Boundary during Kidney Development.Pax2对肾单位祖细胞间质身份的抑制在肾脏发育过程中建立了肾单位-间质边界。
Dev Cell. 2017 May 22;41(4):349-365.e3. doi: 10.1016/j.devcel.2017.04.022.
6
Inhibition of Pax2 Transcription Activation with a Small Molecule that Targets the DNA Binding Domain.用靶向DNA结合结构域的小分子抑制Pax2转录激活
ACS Chem Biol. 2017 Mar 17;12(3):724-734. doi: 10.1021/acschembio.6b00782. Epub 2017 Jan 24.
7
Cap mesenchyme cell swarming during kidney development is influenced by attraction, repulsion, and adhesion to the ureteric tip.肾脏发育过程中帽状间充质细胞的聚集受到对输尿管芽尖的吸引、排斥和黏附作用的影响。
Dev Biol. 2016 Oct 15;418(2):297-306. doi: 10.1016/j.ydbio.2016.06.028. Epub 2016 Jun 23.
8
Growing Kidney Tissue from Stem Cells: How Far from "Party Trick" to Medical Application?利用干细胞培育肾脏组织：从“魔术技巧”到医学应用还有多远？
Cell Stem Cell. 2016 Jun 2;18(6):695-698. doi: 10.1016/j.stem.2016.05.015.
9
Crucial requirement of ERK/MAPK signaling in respiratory tract development.ERK/MAPK信号通路在呼吸道发育中的关键作用。
Development. 2015 Nov 1;142(21):3801. doi: 10.1242/dev.131821.
10
Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.内在的年龄依赖性变化和细胞间接触调节肾单位祖细胞寿命。
Dev Cell. 2015 Oct 12;35(1):49-62. doi: 10.1016/j.devcel.2015.09.009.