Substrates mimicking the blastocyst geometry revert pluripotent stem cell to naivety

IF 37.2 1区材料科学 Q1 CHEMISTRY, PHYSICAL

Nature Materials Pub Date : 2024-08-12 DOI:10.1038/s41563-024-01971-4

Xun Xu, Weiwei Wang, Yue Liu, Johan Bäckemo, Matthias Heuchel, Wei Wang, Yan Nie, Imran Iqbal, Karl Kratz, Andreas Lendlein, Nan Ma

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Abstract

Naive pluripotent stem cells have the highest developmental potential but their in vivo existence in the blastocyst is transient. Here we report a blastocyst motif substrate for the in vitro reversion of mouse and human pluripotent stem cells to a naive state. The substrate features randomly varied microstructures, which we call motifs, mimicking the geometry of the blastocyst. Motifs representing mouse-blastocyst-scaled curvature ranging between 15 and 62 mm−1 were the most efficient in promoting reversion to naivety, as determined by time-resolved correlative analysis. In these substrates, apical constriction enhances E-cadherin/RAC1 signalling and activates the mechanosensitive nuclear transducer YAP, promoting the histone modification of pluripotency genes. This results in enhanced levels of pluripotency transcription factor NANOG, which persist even after cells are removed from the substrate. Pluripotent stem cells cultured in blastocyst motif substrates display a higher development potential in generating embryoid bodies and teratomas. These findings shed light on naivety-promoting substrate design and their large-scale implementation. Substrates with blastocyst-like microstructures effectively revert primed pluripotent stem cells to naivety by promoting cell–cell apical constriction and mechanoinduced epigenetic activation of naive pluripotency genes.

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模拟胚泡几何形状的基质能使多能干细胞恢复天真状态

幼稚多能干细胞具有最高的发育潜能，但它们在体内囊胚中的存在是短暂的。在此，我们报告了一种囊胚图案基底，用于体外将小鼠和人类多能干细胞还原到幼稚状态。这种基底具有随机变化的微结构，我们称之为图案，模仿胚泡的几何形状。通过时间分辨相关分析确定，代表小鼠囊胚尺度曲率（介于 15 至 62 mm-1 之间）的图案在促进干细胞还原至幼稚状态方面最为有效。在这些基质中，顶端收缩增强了E-cadherin/RAC1信号，激活了对机械敏感的核转换器YAP，促进了多能基因的组蛋白修饰。这导致多能性转录因子 NANOG 水平升高，甚至在细胞脱离基质后仍能持续存在。在囊胚图案基质中培养的多能干细胞在生成类胚体和畸胎瘤方面显示出更高的发育潜能。这些发现为天真促进基底的设计及其大规模实施提供了启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Materials 工程技术-材料科学：综合

CiteScore

62.20

自引率

0.70%

发文量

221

审稿时长

3.2 months

期刊介绍： Nature Materials is a monthly multi-disciplinary journal aimed at bringing together cutting-edge research across the entire spectrum of materials science and engineering. It covers all applied and fundamental aspects of the synthesis/processing, structure/composition, properties, and performance of materials. The journal recognizes that materials research has an increasing impact on classical disciplines such as physics, chemistry, and biology. Additionally, Nature Materials provides a forum for the development of a common identity among materials scientists and encourages interdisciplinary collaboration. It takes an integrated and balanced approach to all areas of materials research, fostering the exchange of ideas between scientists involved in different disciplines. Nature Materials is an invaluable resource for scientists in academia and industry who are active in discovering and developing materials and materials-related concepts. It offers engaging and informative papers of exceptional significance and quality, with the aim of influencing the development of society in the future.