美国密歇根大学教授Jianping Fu和Yue Liu共同合作,近期取得重要工作进展。他们研究利用微流控技术建立人类多能干细胞的体节发生模型。相关研究成果2024年7月8日在线发表于《细胞—干细胞》杂志上。
据介绍,新兴的基于人类多能干细胞(hPSC)的胚胎模型可用于研究人类胚胎发生。特别是,有使用自由漂浮培养物的基于hPSC的体节发生模型,可以再现体节的形成。体内的体细胞发生涉及错综复杂的生化和生物力学事件。然而,目前的生长发育模型都不能控制培养物中的生化梯度或生物力学信号,这限制了它们在解开驱动生长发育的复杂生化-生物力学相互作用的适用性。
研究人员通过将hPSC来源的体细胞前中胚层(PSM)组织限制在微加工的沟中,开发了一种人类体细胞发生模型。施加在PSM组织上的外源性微流体形态发生梯度导致轴向模式,并触发自发的从喙部到尾部侧体节形成。发展了一种力学理论来解释体节和PSM之间的尺寸依赖性。微流体体节发生模型被进一步用于,揭示细胞和组织生物力学在体节形成中的调节作用。
总之,这一研究提供了一个有用的基于hPSC的微工程模型,用于理解指导体节形成的生物化学和生物力学事件。
附:英文原文
Title: A human pluripotent stem cell-based somitogenesis model using microfluidics
Author: Yue Liu, Yung Su Kim, Xufeng Xue, Yuchuan Miao, Norio Kobayashi, Shiyu Sun, Robin Zhexuan Yan, Qiong Yang, Olivier Pourquié, Jianping Fu
Issue&Volume: 2024-07-08
Abstract: Emerging human pluripotent stem cell (hPSC)-based embryo models are useful for studyinghuman embryogenesis. Particularly, there are hPSC-based somitogenesis models usingfree-floating culture that recapitulate somite formation. Somitogenesis in vivo involves intricately orchestrated biochemical and biomechanical events. However,none of the current somitogenesis models controls biochemical gradients or biomechanicalsignals in the culture, limiting their applicability to untangle complex biochemical-biomechanicalinteractions that drive somitogenesis. Herein, we develop a human somitogenesis modelby confining hPSC-derived presomitic mesoderm (PSM) tissues in microfabricated trenches.Exogenous microfluidic morphogen gradients imposed on the PSM tissues cause axialpatterning and trigger spontaneous rostral-to-caudal somite formation. A mechanicaltheory is developed to explain the size dependency between somites and the PSM. Themicrofluidic somitogenesis model is further exploited to reveal regulatory roles ofcellular and tissue biomechanics in somite formation. This study presents a usefulmicroengineered, hPSC-based model for understanding the biochemical and biomechanicalevents that guide somite formation.
DOI: 10.1016/j.stem.2024.06.004
Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00212-1
Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:25.269
官方网址:https://www.cell.com/cell-stem-cell/home
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