近日，来自瑞士洛桑联邦理工学院的Matthias P. Lutolf研究组，报道了在体外人工实现人多潜能干细胞空间性分化的新方法。2019年7月出版的《自然—方法学》杂志发表了这一研究进展。

研究人员报道了一种微流控技术，可将人多潜能干细胞（hPSC）集落暴露于人工信号中心产生的具有时空差异的形态发生素梯度中。通过响应局部的BMP4信号，hPSC集落能够打破其原本的辐射对称发育，从而产生截然不同的轴向排列分化区域。与BMP信号相拮抗的NOGGIN信号能够进一步增强这种细胞分化模式的空间性调控。研究人员也探究了形态发生素浓度与细胞密度是如何来影响对BMP信号的响应以及胚层的形成。这些研究结果表明，干细胞在发育过程中自我组织的能力是可以通过使用人工的信号中心来实现的。

据介绍，信号中心是一群分泌形态发生素的细胞，其通过协调细胞命运的空间性分化在早期发育和器官形成中起到关键性作用。

附：英文原文

Title: Engineered signaling centers for the spatially controlled patterning of human pluripotent stem cells

Author: Andrea Manfrin, Yoji Tabata, Eric R. Paquet, Ambroise R. Vuaridel, Franois R. Rivest, Felix Naef, Matthias P. Lutolf

Issue&Volume:Volume 16 Issue 7, July 2019

Abstract: Signaling centers, localized groups of cells that secrete morphogens, play a key role in early development and organogenesis by orchestrating spatial cell fate patterning. Here we present a microfluidic approach that exposes human pluripotent stem cell (hPSC) colonies to spatiotemporally controlled morphogen gradients generated from artificial signaling centers. In response to a localized source of bone morphogenetic protein 4 (BMP4), hPSC colonies reproducibly break their intrinsic radial symmetry to produce distinct, axially arranged differentiation domains. Counteracting sources of the BMP antagonist NOGGIN enhance this spatial control of cell fate patterning. We also show how morphogen concentration and cell density affect the BMP response and germ layer patterning. These results demonstrate that the intrinsic capacity of stem cells for self-organization can be extrinsically controlled through the use of engineered signaling centers.

DOI: 10.1038/s41592-019-0455-2

Source:https://www.nature.com/articles/s41592-019-0455-2