意大利帕多瓦大学Nicola Elvassore研究组发现，三维(3D)细胞外基质(ECM)丰富的环境能够维持原始人iPSCs(hiPSCs)的身份。2022年12月1日出版的《细胞—干细胞》杂志发表了这项成果。

他们使用一种无偏和综合的方法，将微流体培养与转录、蛋白质组和分泌组分析相结合，发现原始hiPSC群体具有自组织的富含ecm的微环境的特征，但是受训hiPSC群体没有。在此基础上，他们开发了一个3D培养系统，该系统支持原始hiPSCs的健壮的长期无馈源自我更新，也允许直接和及时的发育形态发生，只需调节信号环境。他们的研究为未来应用原始hiPSCs从单细胞开始三维研究人类发育的关键阶段开辟了新的视角。

据了解，体外人类多能干细胞培养物的建立为人类发育早期事件的研究开辟了新的视角。几种转录因子和信号通路在维持人类幼稚多能性过程中所起的作用已被证实。然而，人们对ECM及其3D组织所发挥的作用知之甚少。

附：英文原文

Title: 3D ECM-rich environment sustains the identity of naive human iPSCs

Author: Elisa Cesare, Anna Urciuolo, Hannah T. Stuart, Erika Torchio, Alessia Gesualdo, Cecilia Laterza, Onelia Gagliano, Sebastian Martewicz, Meihua Cui, Anna Manfredi, Lucio Di Filippo, Patrizia Sabatelli, Stefano Squarzoni, Irene Zorzan, Riccardo M. Betto, Graziano Martello, Davide Cacchiarelli, Camilla Luni, Nicola Elvassore

Issue&Volume: 2022/12/01

Abstract: The establishment of in vitro naive human pluripotent stem cell cultures opened new perspectives for the studyof early events in human development. The role of several transcription factors andsignaling pathways have been characterized during maintenance of human naive pluripotency.However, little is known about the role exerted by the extracellular matrix (ECM)and its three-dimensional (3D) organization. Here, using an unbiased and integratedapproach combining microfluidic cultures with transcriptional, proteomic, and secretomeanalyses, we found that naive, but not primed, hiPSC colonies are characterized bya self-organized ECM-rich microenvironment. Based on this, we developed a 3D culturesystem that supports robust long-term feeder-free self-renewal of naive hiPSCs andalso allows direct and timely developmental morphogenesis simply by modulating thesignaling environment. Our study opens new perspectives for future applications ofnaive hiPSCs to study critical stages of human development in 3D starting from a singlecell.

DOI: 10.1016/j.stem.2022.11.011

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00458-1