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| Status |
Public on May 13, 2020 |
| Title |
Human Naive Pluripotency Attained by Transient Inhibition of mTOR |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Mouse embryonic stem cells (mESCs) are in naive pluripotency that represents the ground state of development, from which all cells in the mouse embryo are derived. In contrast, human embryonic stem cells (hESCs) are in a primed state of pluripotency with many different properties. Despite intense efforts to generate naive human pluripotent stem cells (hPSCs), it has not been possible to derive naive hPSCs without relying on transgene overexpression or chemicals. Here, we show that a transient treatment with Torin1, a selective inhibitor of mTOR, converted hPSCs from primed to naive pluripotency. The naive hPSCs were maintained in the same condition as mESCs in defined media with 2iLI (MEK inhibitor, GSK3b inhibitor, LIF and Insulin). Like mESCs, they exhibited high clonal efficiency, rapid cell proliferation, active mitochondrial respiration, X chromosome activation, DNA hypomethylation, and transcriptomes similar to those of human blastocysts than primed hESCs. Most importantly, the naive hPSCs significantly contributed to mouse embryos when transferred to mouse blastocysts. mTor inhibition induced nuclear translocation of TFE3, a critical transcription factor at the interplay of autophagy and pluripotency. TFE3 with mutated nuclear localization signal blocked the conversion from primed to naive pluripotency. It appears that by mimicking diapause at the cellular level, naive pluripotency in human can be readily attained from primed hPSCs, thus establishing the unified ground state of pluripotency in mammals.
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| Overall design |
Comparison of DNA methylation signature between primed state and naïve state PSCs.
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| Contributor(s) |
Hu Z, Li H, Jiang H, Ren Y, Yu X, Qiu J, Stablewski AB, Zhang B, Buck MJ, Feng J |
| Citation(s) |
32426495 |
| Submission date |
Jul 28, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Jian Feng |
| E-mail(s) |
jianfeng@buffalo.edu
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| Phone |
716-829-2345
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| Organization name |
State University of New York at Buffalo
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| Department |
Department of Physiology and Biophysics
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| Lab |
Feng Lab
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| Street address |
955 Main Street, Room 3102
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| City |
Buffalo |
| State/province |
NY |
| ZIP/Postal code |
14203 |
| Country |
USA |
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| Platforms (1) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA396242 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE102031_RAW.tar |
385.1 Mb |
(http)(custom) |
TAR (of IDAT) |
| Processed data included within Sample table |
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