Plakoglobin is a mechanoresponsive regulator of naive pluripotency.
Plakoglobin is a mechanoresponsive regulator of naive pluripotency.
复制标题
DOI：
10.1038/s41467-023-39515-0
复制
发表时间：
2023-07-07
影响因子：
16.6
通讯作者：
Hollfelder, Florian
中科院分区：
文献类型：
--
作者：
Kohler, Timo N.;De Jonghe, Joachim;Ellermann, Anna L.;Yanagida, Ayaka;Herger, Michael;Slatery, Erin M.;Weberling, Antonia;Munger, Clara;Fischer, Katrin;Mulas, Carla;Winkel, Alex;Ross, Connor;Bergmann, Sophie;Franze, Kristian;Chalut, Kevin;Nichols, Jennifer;Boroviak, Thorsten E.;Hollfelder, Florian
生物力学线索是指导胚胎发育和细胞分化的工具。了解这些物理刺激如何转化为转录程序将有助于深入了解哺乳动物着床前发育的机制。在这里，我们通过对小鼠胚胎干细胞施加微环境控制来探索这种类型的调节。用琼脂糖微凝胶对小鼠胚胎干细胞进行微流体封装，稳定了初始多能性网络，并特异性诱导了血小板蛋白（plakhemoglobin, Jup）的表达，这是一种脊椎动物β-连环蛋白的同源物。正如单细胞转录组谱所证实的那样，在亚稳态多能性条件下，过表达plakhemoglobin足以完全重建初始多能性基因调控网络。最后，我们发现，在人类和小鼠胚胎的外胚层中，血小板红蛋白仅在囊胚阶段表达，这进一步加强了血小板红蛋白与体内初始多能性之间的联系。我们的工作揭示了血小板红蛋白作为一种机械敏感的原始多能性调节剂，并提供了一个范式来询问体积限制对细胞命运转变的影响。机械微环境影响干细胞的多能性。在这里，作者在控制体积限制的微凝胶中培养干细胞，并鉴定出血小板红蛋白是小鼠和人类多能性的机械反应调节因子。
Biomechanical cues are instrumental in guiding embryonic development and cell differentiation. Understanding how these physical stimuli translate into transcriptional programs will provide insight into mechanisms underlying mammalian pre-implantation development. Here, we explore this type of regulation by exerting microenvironmental control over mouse embryonic stem cells. Microfluidic encapsulation of mouse embryonic stem cells in agarose microgels stabilizes the naive pluripotency network and specifically induces expression of Plakoglobin (Jup), a vertebrate homolog of β-catenin. Overexpression of Plakoglobin is sufficient to fully re-establish the naive pluripotency gene regulatory network under metastable pluripotency conditions, as confirmed by single-cell transcriptome profiling. Finally, we find that, in the epiblast, Plakoglobin was exclusively expressed at the blastocyst stage in human and mouse embryos – further strengthening the link between Plakoglobin and naive pluripotency in vivo. Our work reveals Plakoglobin as a mechanosensitive regulator of naive pluripotency and provides a paradigm to interrogate the effects of volumetric confinement on cell-fate transitions. The mechanical microenvironment influences stem cell pluripotency. Here, the authors culture stem cells in microgels with controlled volumetric confinement and identify Plakoglobin as a mechanoresponsive regulator of pluripotency in mouse and human.
登录
查看更多内容
影响因子：
21.3
作者：
Boroviak T;Loos R;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
影响因子：
3.7
作者：
Mahendram S;Kelly KF;Paez-Parent S;Mahmood S;Polena E;Cooney AJ;Doble BW
通讯作者：
Doble BW
影响因子：
23.9
作者：
De Belly H;Stubb A;Yanagida A;Labouesse C;Jones PH;Paluch EK;Chalut KJ
通讯作者：
Chalut KJ
DOI：
10.1083/jcb.118.3.671
发表时间：
1992-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Knudsen KA;Wheelock MJ
通讯作者：
Wheelock MJ
影响因子：
3.7
作者：
Chowdhury F;Li Y;Poh YC;Yokohama-Tamaki T;Wang N;Tanaka TS
通讯作者：
Tanaka TS