ISRIB facilitates the co-culture of human trophoblast stem cells and embryonic stem cells

Shuwei Xia, Dainan Yu, Yue Wang, Beijia He, Yin Rong, Shuo Chen, Zhenyu Xiao, Hongmei Wang, Hao Wu*, Long Yan*

*此作品的通讯作者

科研成果: 期刊稿件文章同行评审

摘要

The embryo-like structures (embryoids) constructed by aggregating embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) have provided revolutionary tools for studying the intricate interaction between embryonic and extra-embryonic tissues during early embryonic development, which has been achieved in mice. However, due to the opposite dependence on some signalling pathways for in vitro culture of human ESCs (hESCs) and TSCs (hTSCs), particularly WNT and TGFβ signalling pathways, which limits the construction of human post-implantation embryoids by aggregating hESCs and hTSCs. To overcome this challenge, here, by screening 1639 chemicals, we found that an inhibitor of integrated stress response, ISRIB, can replace WNT agonists and TGFβ inhibitors to maintain the stemness and differentiation capacity of hTSCs. Thus, we developed an ISRIB-dependent in vitro culture medium for hTSCs, namely nTSM. Furthermore, we demonstrated that ISRIB could also maintain the hESC stemness. Using a 3D co-culture system (hESCs and hTSCs aggregate, ETA), we demonstrated that a 1:1 mixture of hESC culture medium (ESM) and nTSM improved the cell proliferation and organisation of both hESC- and hTSC-compartments and the lumenogenesis of hESC-compartment in ETAs. Overall, our study provided an ISRIB-dependent system for co-culturing hESCs and hTSCs, which facilitated the construction of human embryoids by aggregating hESCs and hTSCs.

源语言英语
文章编号e13599
期刊Cell Proliferation
57
6
DOI
出版状态已出版 - 6月 2024

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Xia, S., Yu, D., Wang, Y., He, B., Rong, Y., Chen, S., Xiao, Z., Wang, H., Wu, H., & Yan, L. (2024). ISRIB facilitates the co-culture of human trophoblast stem cells and embryonic stem cells. Cell Proliferation, 57(6), 文章 e13599. https://doi.org/10.1111/cpr.13599