Deng Hongkui and Li Cheng cooperate to establish a new type of totipotent stem cells with the ability to form blastocysts using mouse two-cell embryos

On May 4, 2022, Professor Deng Hongkui's research group and researcher Li Cheng's research group from Peking University School of Life Sciences, Peking University-Tsinghua Life Science Joint Center, and researcher Xu Jun's research group from the School of Basic Medicine, Peking University published a title in the journal Cell Researc.

For the research paper of " Derivation of totipotent-like stem cells with blastocyst-like structure forming potential.

This study established a new totipotent stem cell culture condition through a combination of chemical small molecule screening, which can support the establishment of totipotent stem cell lines from mouse two-cell embryos and expanded pluripotent stem cells (EPS cell.

This novel totipotent stem cell can be stably cultured for a long time in vitro, is highly similar to mouse two-cell embryos in molecular characteristics and developmental potential, and can be induced in vitro to form blastocysts that are similar to blastocysts in vivo at the transcriptomic level structu.

Screenshot of the paper

How to prepare totipotent stem cells in vitro has long been an important scientific issue in the field of stem cel.

In mice, only fertilized eggs and two-cell embryos are totipotent: a single cell can form a fully-living individu.

The subsequently developed blastocyst cells can be used to establish pluripotent stem cells, trophoblast stem cells and primitive endoderm stem cel.

However, the developmental potential of these stem cells is limited and cannot develop into both intraembryonic and extraembryonic tissu.

Recent studies have found that there are very few cells expressing the mouse two-cell embryo molecular marker MERVL in the mouse pluripotent stem cell population, which are called two-cell-like cells (2-celllike cells), and have some molecules of two-cell embry.

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However, such cells cannot be stably cultured in vit.

In addition, recent studies have found that two-cell-like cells are still quite different from two-cell embryos in vivo, and there are still great limitations as a model for studying totipotency in vitro ⁽²⁾

Deng Hongkui's team at Peking University has long been committed to establishing new methods for regulating the developmental potential of stem cells by means of chemical small molecule regulation ^(3-6)

In 2017, Deng Hongkui's team reported a new small molecule combination (LCDM) that can establish expanded pluripotent stem cells (EPS cells) in humans and mice ⁽⁴⁾

In this study, the team identified chemical small molecules that could induce an increase in the proportion of MERVL and Zscan4 positive cells in EPS cells through high-throughput screening of chemical small molecul.

The researchers further analyzed the molecular characteristics and developmental potential of TPS cells from the aspects of transcriptome, epigenetic characteristics and chimeric abili.

The ability to self-assemble into blastocyst-like structures is one of the most critical functional criteria for assessing cell totipoten.

Finally, we analyzed the molecular mechanism by which CPEC combination induces and regulates totipotency in TPS cel.

In conclusion, this study established a new type of totipotent stem cells from mouse two-cell embryos by chemical regulati.

Deng Hongkui, Li Cheng and Xu Jun are the co-corresponding authors of the pap.

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