期刊
STEM CELL REPORTS
卷 13, 期 3, 页码 485-498出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2019.07.011
关键词
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资金
- RIKEN
- Kyoto University
- Gladstone Institutes
- L. K. Whittier Foundation
- Roddenberry Foundation
- National Heart, Lung, and Blood Institute/NIH [U01-HL100406, U01-HL098179]
- California Institute for Regenerative Medicine (CIRM)
- National Center for Research Resources [RR18928-01]
- RIKEN SPDR program
- JSPS KAKENHI [17K07246]
- Suzuki Memorial Foundation
- OMC Internal Research Grant
- Yamanaka lab
- Takahashi lab
- Grants-in-Aid for Scientific Research [17K07246] Funding Source: KAKEN
Soon after fertilization, the few totipotent cells of mammalian embryos diverge to form a structure called the blastocyst (BC). Although numerous cell types, including germ cells and extended-pluripotency stem cells, have been developed from pluripotent stem cells (PSCs) in vitro, generating functional BCs only from PSCs remains elusive. Here, we describe induced self-organizing 3D BC-like cysts (iBLCs) generated from mouse PSC culture. Resembling natural BCs, iBLCs have a blastocoel-like cavity and were formed with outer cells expressing trophectoderm lineage markers and with inner cells expressing pluripotency markers. iBLCs transplanted to pseudopregnant mice uteruses implanted, induced decidualization, and exhibited growth and development before resorption, demonstrating that iBLCs are implantation competent. iBLC precursor intermediates required the transcription factor Prdm14 and concomitantly activated the totipotency-related cleavage-stage MERVL reporter and 2C genes. Thus, our system may contribute to the understanding of molecular mechanisms underpinning totipotency, embryogenesis, and implantation.
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