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通过使用数字体积相关技术的四维研究揭示三维人类结肠类器官中的有丝分裂纺锤体方向如何影响基质位移。

Unveiling how mitotic spindle orientation in 3D human colon organoids affects matrix displacements through a 4D study using DVC.

作者信息

Magne L, Pottier T, Michel D, Laussu J, Bonnet D, Alric L, Segonds S, Recher G, Bugarin F, Ferrand A

机构信息

Institut de Recherche en Santé Digestive, Université de Toulouse, INSERM, INRAE, ENVT, UPS, U1220, CHU Purpan, CS60039, Toulouse, 31024, France.

Institut Clément Ader, Université Fédérale de Toulouse Midi-Pyrénées, CNRS, UPS, INSA, ISAE-SUPAERO, IMT Mines Albi, 3, rue Caroline Aigle, Toulouse, 31400, France.

出版信息

Sci Rep. 2025 Jul 1;15(1):22052. doi: 10.1038/s41598-025-04156-4.

DOI:10.1038/s41598-025-04156-4
PMID:40595987
Abstract

Cell division is a major event in tissue homeostasis, enabling renewal and regeneration. In human colon, vertical division is mainly observed in the stem cell compartment while horizontal division is more frequent in the progenitor transit amplifying zone. To study cell division, the human colon epithelium represents a relevant model due to its rapid renewal and high number of mitoses. Studying live mechanical interactions between the epithelium and its matrix in vivo is challenging due to the lack of suitable methods. Colon organoids seeded in Matrigel are good models because they recapitulate the organization and properties of tissue architecture. This culture set-up allows to study the displacements of the matrix around the organoid. We studied the impact of cell division within the human colonic epithelium on the extracellular matrix. We validated an original experimental and analytical process with 3D time-lapse confocal microscopy to follow cell division and matrix displacements, on which we performed a 4D Digital Volume Correlation. Depending on the orientation of the mitotic spindle, cell division affects the matrix differently. Vertical division causes a predominantly uniaxial displacement of the matrix, while horizontal division involves a multiaxial and wider displacement.

摘要

细胞分裂是组织稳态中的一个重大事件,能够实现更新和再生。在人类结肠中,垂直分裂主要出现在干细胞区室,而水平分裂在祖细胞过渡扩增区更为频繁。由于人类结肠上皮更新迅速且有大量有丝分裂,因此它是研究细胞分裂的一个相关模型。由于缺乏合适的方法,在体内研究上皮与其基质之间的实时力学相互作用具有挑战性。接种在基质胶中的结肠类器官是很好的模型,因为它们概括了组织结构的组织形式和特性。这种培养设置允许研究类器官周围基质的位移。我们研究了人类结肠上皮内的细胞分裂对细胞外基质的影响。我们用三维延时共聚焦显微镜验证了一个原始的实验和分析过程,以跟踪细胞分裂和基质位移,并在此基础上进行了四维数字体积相关分析。根据有丝分裂纺锤体的方向,细胞分裂对基质的影响不同。垂直分裂导致基质主要发生单轴位移,而水平分裂涉及多轴且更广泛的位移。

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本文引用的文献

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Deciphering the interplay between biology and physics with a finite element method-implemented vertex organoid model: A tool for the mechanical analysis of cell behavior on a spherical organoid shell.用有限元法实现的顶点类器官模型解析生物学与物理学之间的相互作用:一种用于分析球形类器官壳上细胞行为的力学工具。
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Length limitation of astral microtubules orients cell divisions in murine intestinal crypts.
星体微管的长度限制决定了小鼠肠道隐窝中的细胞分裂方向。
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Stiffness Restricts the Stemness of the Intestinal Stem Cells and Skews Their Differentiation Toward Goblet Cells.僵硬限制了肠干细胞的干性,并使其向杯状细胞分化发生偏倚。
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Regulation and functions of cell division in the intestinal tissue.肠道组织中的细胞分裂调控与功能。
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Digesting the mechanobiology of the intestinal epithelium.解析肠道上皮细胞的机械生物学
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