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人胰腺导管类器官中的旋转迁移取决于肌动蛋白和肌球蛋白的活性。

Rotational migration in human pancreatic ductal organoids depends on actin and myosin activity.

作者信息

Xie Gengqiang, Modak Chaity, Usman Olalekan H, Tan Raphael W F, Coca Nicole, De Jesus Gabriela, Wang Yue Julia, Thirumalai D, Li Xin, Irianto Jerome

机构信息

Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA.

Department of Chemistry, University of Texas at Austin, Austin, TX, USA.

出版信息

Commun Biol. 2025 Dec 5;8(1):1749. doi: 10.1038/s42003-025-09136-y.

DOI:10.1038/s42003-025-09136-y
PMID:41350596
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12680755/
Abstract

Rotational migration is one specific form of collective cell migration when epithelial cells are confined in a spherical geometry, such as in the epithelial acini. This tissue-level rotation motion is crucial for the morphogenesis of multiple epithelial systems. Here, we introduce human pancreatic ductal organoids as a model to study rotational migration. Live imaging revealed the persistent rotation of the organoids over time. By tracking the nuclei, the three-dimensional trajectory of the cellular movement was reconstructed and the velocity of the rotation was quantified. The presence of focal adhesion clusters and prominent actin stress fibers were observed at the basal side of the organoids, suggesting the interactions between the cells and the surrounding extracellular matrix. Finally, our inhibition study showed the dependence of pancreatic ductal organoid rotational migration on myosin activity, actin polymerization, and actin branching. We hope that this model will enable future studies with human primary cells, which are more faithful to normal epithelial cells.

摘要

旋转迁移是上皮细胞被限制在球形结构中(如上皮腺泡)时集体细胞迁移的一种特定形式。这种组织水平的旋转运动对多个上皮系统的形态发生至关重要。在此,我们引入人胰腺导管类器官作为研究旋转迁移的模型。实时成像显示类器官随时间持续旋转。通过追踪细胞核,重建了细胞运动的三维轨迹并量化了旋转速度。在类器官的基底侧观察到粘着斑簇和明显的肌动蛋白应力纤维的存在,表明细胞与周围细胞外基质之间的相互作用。最后,我们的抑制研究表明胰腺导管类器官的旋转迁移依赖于肌球蛋白活性、肌动蛋白聚合和肌动蛋白分支。我们希望这个模型将有助于未来对人原代细胞的研究,这些细胞更接近正常上皮细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6672/12680755/1d7e527d3e03/42003_2025_9136_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6672/12680755/441b11c62856/42003_2025_9136_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6672/12680755/dfd041f7c1a4/42003_2025_9136_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6672/12680755/65fd93ba2918/42003_2025_9136_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6672/12680755/33ab0844a5d4/42003_2025_9136_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6672/12680755/1d7e527d3e03/42003_2025_9136_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6672/12680755/441b11c62856/42003_2025_9136_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6672/12680755/dfd041f7c1a4/42003_2025_9136_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6672/12680755/65fd93ba2918/42003_2025_9136_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6672/12680755/33ab0844a5d4/42003_2025_9136_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6672/12680755/1d7e527d3e03/42003_2025_9136_Fig5_HTML.jpg

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本文引用的文献

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Nat Biomed Eng. 2024 Dec 10. doi: 10.1038/s41551-024-01273-9.
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Lumen expansion is initially driven by apical actin polymerization followed by osmotic pressure in a human epiblast model.腔扩张最初是由人上胚层模型中的顶端肌动蛋白聚合驱动,随后是渗透压。
Cell Stem Cell. 2024 May 2;31(5):640-656.e8. doi: 10.1016/j.stem.2024.03.016.
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TGF-β signaling in health, disease, and therapeutics.
TGF-β 信号在健康、疾病和治疗中的作用。
Signal Transduct Target Ther. 2024 Mar 22;9(1):61. doi: 10.1038/s41392-024-01764-w.
4
Activation of ductal progenitor-like cells from adult human pancreas requires extracellular matrix protein signaling.从成人胰腺中激活导管祖细胞样细胞需要细胞外基质蛋白信号传导。
iScience. 2024 Feb 15;27(3):109237. doi: 10.1016/j.isci.2024.109237. eCollection 2024 Mar 15.
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Differential modulation of cellular phenotype and drug sensitivity by extracellular matrix proteins in primary and metastatic pancreatic cancer cells.细胞外基质蛋白对原代和转移性胰腺癌细胞表型和药物敏感性的差异调节。
Mol Biol Cell. 2023 Dec 1;34(13):ar130. doi: 10.1091/mbc.E23-02-0075. Epub 2023 Oct 30.
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Fat2 polarizes Lar and Sema5c to coordinate the motility of collectively migrating epithelial cells.脂肪 2 使 Lar 和 Sema5c 极化,以协调集体迁移上皮细胞的运动。
J Cell Sci. 2024 Mar 1;137(5). doi: 10.1242/jcs.261173. Epub 2023 Sep 11.
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Curvature induces active velocity waves in rotating spherical tissues.曲率诱导旋转球体组织中的主动速度波。
Nat Commun. 2023 Mar 24;14(1):1643. doi: 10.1038/s41467-023-37054-2.
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Methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts.甲基纤维素集落测定和单细胞微操作揭示成人胰腺导管中的祖细胞样细胞。
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