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Inhibition of mTOR induces a paused pluripotent state
Open accessAbstract
Cultured pluripotent stem cells are a cornerstone of regenerative medicine owing to their ability to give rise to all cell types of the body. Although pluripotent stem cells can be propagated indefinitely in vitro, pluripotency is paradoxically a transient state in vivo, lasting 2-3 days around the time of blastocyst implantation. The exception to this rule is embryonic diapause, a reversible state of suspended development triggered by unfavourable conditions. Diapause is a physiological reproductive strategy widely employed across the animal kingdom, including in mammals, but its regulation remains poorly understood. Here we report that the partial inhibition of mechanistic target of rapamycin (mTOR), a major nutrient sensor and promoter of growth, induces reversible pausing of mouse blastocyst development and allows their prolonged culture ex vivo. Paused blastocysts remain pluripotent and competent-able to give rise to embryonic stem (ES) cells and live, fertile mice. We show that both naturally diapaused blastocysts in vivo and paused blastocysts ex vivo display pronounced reductions in mTOR activity, translation, histone modifications associated with gene activity and transcription. Pausing can be induced directly in cultured ES cells and sustained for weeks without appreciable cell death or deviations from cell cycle distributions. We show that paused ES cells display a remarkable global suppression of transcription, maintain a gene expression signature of diapaused blastocysts and remain pluripotent. These results uncover a new pluripotent stem cell state corresponding to the epiblast of the diapaused blastocyst and indicate that mTOR regulates developmental timing at the peri-implantation stage. Our findings have implications in the fields of assisted reproduction, regenerative medicine, cancer, metabolic disorders and ageing.
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“Similar intermediate states have been described during embryonic development, where cells enter a paused, pluripotent state in response to environmental stress.62”
From Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer (2026) · cites this paper as [62]
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“For example, of the 131 cells that undergo apoptosis in C. elegans, the great majority (105) are neurons, thus highlighting the importance of PCD for CNS development.22”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [22]
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“Lysosomes are also important in apoptosis, a form of programmed cell death (PCD) that is requisite for the appropriate development of the mammalian nervous system.21,22.”
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Cites
KEGG: Kyoto Encyclopedia of Genes and Genomes
Kanehisa, M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.27 · Cited by 37,077
KEGG: Kyoto Encyclopedia of Genes and Genomes
Ogata, H., Goto, S., Sato, K., Fujibuchi, W., Bono, H., & Kanehisa, M. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.29 · Cited by 31,232
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668
Establishment in culture of pluripotential cells from mouse embryos
Evans, M. J., & Kaufman, M. H. (1981) · Nature · doi:10.1038/292154a0 · Cited by 8,623
CellProfiler: image analysis software for identifying and quantifying cell phenotypes
Carpenter, A. E., Jones, T. R., Lamprecht, M. R., Clarke, C., Kang, I. H., Friman, O., Guertin, D. A., Chang, J. H., Lindquist, R. A., Moffat, J., et al. (2006) · Genome biology · doi:10.1186/gb-2006-7-10-r100 · Cited by 5,212
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
Gene Ontology Consortium: going forward
The Gene Ontology Consortium (2015) · Nucleic Acids Research · doi:10.1093/nar/gku1179 · Cited by 3,492
The ground state of embryonic stem cell self-renewal
Ying, Q.-L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., Cohen, P., & Smith, A. (2008) · Nature · doi:10.1038/nature06968 · Cited by 3,442
Derivation of completely cell culture-derived mice from early-passage embryonic stem cells.
Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W., & Roder, J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.18.8424 · Cited by 2,328
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Rehman, S. K., Haynes, J., Collignon, E., Brown, K. R., Wang, Y., Nixon, A. M. L., Bruce, J. P., Wintersinger, J. A., Singh Mer, A., Lo, E. B. L., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.018 · Cited by 495
Self-citationMetabolic signatures of cancer cells and stem cells
Intlekofer, A. M., & Finley, L. W. S. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0032-0 · Cited by 322
Tracking the embryonic stem cell transition from ground state pluripotency
Kalkan, T., Olova, N. N., Roode, M., Mulas, C., Lee, H. J., Nett, I., Marks, H., Walker, R. V., Stunnenberg, H. G., Lilley, K. S., et al. (2017) · Development · doi:10.1242/dev.142711 · Cited by 295
Dhimolea, E., Simoes, R. D. M., Kansara, D. N., Al’Khafaji, A. M., Bouyssou, J., Weng, X., Sharma, S., Raja, J., Awate, P., Shirasaki, R., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2020.12.002 · Cited by 268
Deconstructing and reconstructing the mouse and human early embryo
Shahbazi, M. N., & Zernicka‐Goetz, M. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0144-x · Cited by 227
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Russo, M., Chen, M., Mariella, E., Peng, H., Rehman, S. K., Sancho, E., Sogari, A., Toh, T. S., Balaban, N. Q., Batlle, E., et al. (2024) · Nature Reviews Cancer · doi:10.1038/s41568-024-00737-z · Cited by 210
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Renfree, M. B., & Fenelon, J. C. (2017) · Development · doi:10.1242/dev.148213 · Cited by 204
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Meng, D., Frank, A. R., & Jewell, J. L. (2018) · Development · doi:10.1242/dev.152595 · Cited by 201
Translational control of stem cell function
Saba, J. A., Liakath‐Ali, K., Green, R., & Watt, F. M. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00386-2 · Cited by 205
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Macrae, T. A., Fothergill-Robinson, J., & Ramalho‐Santos, M. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00518-2 · Cited by 196
Self-citationMetabolism in Pluripotent Stem Cells and Early Mammalian Development
Zhang, J., Zhao, J., Dahan, P., Lu, V., Zhang, C., Li, H., & Teitell, M. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.01.008 · Cited by 164
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Zhao, J., Yao, K., Yu, H., Zhang, L., Xu, Y., Chen, L., Sun, Z., Zhu, Y., Zhang, C., Qian, Y., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00464-x · Cited by 167
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Mathieu, J., & Ruohola‐Baker, H. (2017) · Development · doi:10.1242/dev.128389 · Cited by 147
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Yang, P., Humphrey, S. J., Cinghu, S., Pathania, R., Oldfield, A. J., Kumar, D., Perera, D., Yang, J. Y. H., James, D. E., Mann, M., et al. (2019) · Cell Systems · doi:10.1016/j.cels.2019.03.012 · Cited by 146
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Bowling, S., Gregorio, A. D., Sancho, M., Pozzi, S., Aarts, M., Signore, M., Schneider, M. D., Martı́nez-Barberá, J. P., Gil, J., & Rodríguez, T. A. (2018) · Nature Communications · doi:10.1038/s41467-018-04167-y · Cited by 127
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Li, M., & Belmonte, J. C. I. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0067-6 · Cited by 124
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Liu, J., Liu, C., Zhang, J., Zhang, Y., Liu, K., Song, J., Sreenivasmurthy, S. G., Wang, Z., Shi, Y., Chu, C., et al. (2020) · ACS Nano · doi:10.1021/acsnano.9b06453 · Cited by 117
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Self-citationWright, S. C. E., Vasilevski, N., Serra, V., Rodon, J. A., & Eichhorn, P. J. A. (2021) · Cancers · doi:10.3390/cancers13071538 · Cited by 116
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Villegas, F., Lehalle, D., Mayer, D., Rittirsch, M., Stadler, M. B., Zinner, M., Olivieri, D., Vabres, P., Duplomb-Jego, L., De Bont, E. S. J. M., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2018.11.021 · Cited by 110
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Gabut, M., Bourdelais, F., & Durand, S. (2020) · Cells · doi:10.3390/cells9020497 · Cited by 106
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Teixeira, F. K., & Lehmann, R. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a032987 · Cited by 96
Bulut-Karslioglu, A., Macrae, T. A., Oses-Prieto, J. A., Covarrubias, S., Percharde, M., Ku, G., Diaz, A., McManus, M. T., Burlingame, A. L., & Ramalho-Santos, M. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.02.004 · Cited by 97
Self-citationLi, M., Yu, J., Tilgner, K., Ong, S. H., Koike-Yusa, H., & Yusa, K. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.027 · Cited by 96
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Tahmasebi, S., Amiri, M., & Sonenberg, N. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2018.00709 · Cited by 94
Kime, C., Kiyonari, H., Ohtsuka, S., Kohbayashi, E., Asahi, M., Yamanaka, S., Takahashi, M., & Tomoda, K. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.07.011 · Cited by 87
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Corsini, N. S., Peer, A. M., Möseneder, P., Roiuk, M., Burkard, T. R., Theussl, H., Moll, I., & Knoblich, J. A. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.03.002 · Cited by 79
Norrmén, C., Figlia, G., Pfistner, P., Pereira, J. A., Bachofner, S., & Suter, U. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.3619-17.2018 · Cited by 74
Hu, Z., Li, H., Jiang, H., Ren, Y., Yu, X., Qiu, J., Stablewski, A. B., Zhang, B., Buck, M. J., & Feng, J. (2020) · Science Advances · doi:10.1126/sciadv.aaz0298 · Cited by 72
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Fenelon, J. C., & Renfree, M. B. (2018) · Biology of Reproduction · doi:10.1093/biolre/ioy112 · Cited by 70
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Zhang, Z., Hou, H., Yu, S., Zhou, C., Zhang, X., Li, N., Zhang, S., Song, K., Lü, Y., Liu, D., et al. (2019) · Glia · doi:10.1002/glia.23707 · Cited by 64
Liu, Y., Azizian, N. G., Sullivan, D. K., & Li, Y. (2022) · Nature Communications · doi:10.1038/s41467-022-34890-6 · Cited by 68
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de Magalhães, J. P. (2023) · Genome biology · doi:10.1186/s13059-023-02888-y · Cited by 71
Khoa, L. T. P., Tsan, Y.-C., Mao, F., Kremer, D. M., Sajjakulnukit, P., Zhang, L., Zhou, B. O., Tong, X., Bhanu, N. V., Choudhary, C., et al. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.06.005 · Cited by 62
Lynch, C. J., Bernad, R., Martínez‐Val, A., Shahbazi, M. N., Pereira, S. N., Calvo, I., Blanco‐Aparicio, C., Tarantino, C., Garreta, E., Richart, L., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0573-1 · Cited by 65
The mTOR pathway in reproduction: from gonadal function to developmental coordination
Correia, B., Sousa, M. I., & Ramalho‐Santos, J. (2019) · Reproduction · doi:10.1530/rep-19-0057 · Cited by 65
Fan, R., Kim, Y. S., Wu, J., Chen, R., Zeuschner, D., Mildner, K., Adachi, K., Wu, G., Galatidou, S., Li, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19353-0 · Cited by 58
Liu, J., Niu, N., Li, X., Zhang, X., & Sood, A. K. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.10.005 · Cited by 63
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Bora, P., Gahurová, L., Mašek, T., Hauserová, A., Potěšil, D., Jansová, D., Šušor, A., Zdráhal, Z., Ajduk, A., Pospíšek, M., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02290-z · Cited by 55
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Huyghe, A., Furlan, G., Ozmadenci, D., Galonska, C., Charlton, J., Gaume, X., Combémorel, N., Riemenschneider, C., Allègre, N., Zhang, J., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0483-2 · Cited by 55
Liu, W. M., Cheng, R. R., Niu, Z., Chen, A. C. H., Y., M., Li, T., Chiu, P. C. N., Pang, R. T., Lee, Y. L., Ou, J., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz7070 · Cited by 55
Keller, A., Dziedzicka, D., Zambelli, F., Markouli, C., Sermon, K., Spits, C., & Geens, M. (2017) · Human Reproduction Update · doi:10.1093/humupd/dmx042 · Cited by 51
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Liu, X., Peng, S., Tang, G., Xu, G., Xie, Y., Shen, D., Zhu, M., Huang, Y., Wang, X., Yu, H., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104496 · Cited by 52
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Mathieu, J., Detraux, D., Kuppers, D. A., Wang, Y., Cavanaugh, C., Sidhu, S. B., Levy, S., Robitaille, A. M., Ferreccio, A., Bottorff, T., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08020-0 · Cited by 52
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Easwaran, S., & Montell, D. J. (2023) · Biochemical Society Transactions · doi:10.1042/bst20221431 · Cited by 44
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Chen, Q., & Hu, G. (2017) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2017.06.010 · Cited by 35
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Suvorova, I. I., Knyazeva, A. R., Petukhov, A. V., Aksenov, N. D., & Pospelov, V. A. (2019) · Cell Death Discovery · doi:10.1038/s41420-019-0137-y · Cited by 40
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Kamemizu, C., & Fujimori, T. (2019) · Biology of Reproduction · doi:10.1093/biolre/ioz017 · Cited by 40
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Ibayashi, M., Aizawa, R., Mitsui, J., & Tsukamoto, S. (2021) · Reproduction · doi:10.1530/rep-21-0238 · Cited by 42
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Lu, V., Roy, I. J., & Teitell, M. A. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.09.013 · Cited by 40
Lv, G., Wang, Q., Lin, L., Ye, Q., Li, X., Zhou, Q., Kong, X., Deng, H., You, F., Chen, H., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01473-0 · Cited by 40
m6A RNA methylation orchestrates transcriptional dormancy during paused pluripotency
Collignon, É., Cho, B., Furlan, G., Fothergill-Robinson, J., Martin, S.-B., McClymont, S. A., Ross, R. L., Limbach, P. A., & Ramalho‐Santos, M. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01212-x · Cited by 34
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Yan, H., Malik, N., Kim, Y., He, Y., Li, M., Dubois, W., Liu, H., Peat, T. J., Nguyen, J. T., Tseng, Y., et al. (2021) · EMBO Reports · doi:10.15252/embr.202052122 · Cited by 33
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van der Weijden, V. A., & Bulut-Karslıoğlu, A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.708318 · Cited by 35
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Sabino, J. C., de Almeida, M. R., Abreu, P. L., Ferreira, A. M., Caldas, P., Domingues, M. M., Santos, N. C., Azzalin, C. M., Grosso, A. R., & de Almeida, S. F. (2022) · eLife · doi:10.7554/elife.69476 · Cited by 32
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Chen, X., Lu, Y., Wang, L., Ma, X., Pu, J., Lin, L., Deng, Q., Li, Y., Wang, W., Jin, Y. J., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01193-x · Cited by 32
Loss of foxo rescues stem cell aging in Drosophila germ line
Artoni, F., Kreipke, R. E., Palmeira, O., Dixon, C., Goldberg, Z. H., & Ruohola‐Baker, H. (2017) · eLife · doi:10.7554/elife.27842 · Cited by 29
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Zhang, L., Wang, X., Wang, Z., Li, K., Xu, B., & Zhang, J. (2019) · Molecular Medicine Reports · doi:10.3892/mmr.2019.10193 · Cited by 30
Moniz, I., Ramalho‐Santos, J., & Branco, A. F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073749 · Cited by 27
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Ye, J., Jin, H., Pankov, A., Song, J. S., & Blelloch, R. H. (2017) · RNA · doi:10.1261/rna.061499.117 · Cited by 28
Self-citationRamponi, V., Richart, L., Kovatcheva, M., Attolini, C. S., Capellades, J., Lord, A. E., Yanes, Ó., Ficz, G., & Serrano, M. (2024) · Cancer Research · doi:10.1158/0008-5472.can-24-0529 · Cited by 29
El-Sheikh, M., Mesalam, A. A., Idrees, M., Sidrat, T., Mesalam, A., Lee, K., & Kong, I. (2020) · Cells · doi:10.3390/cells9061550 · Cited by 26
Kim, Y., Cho, B., Cook, D. P., Trcka, D., Wrana, J. L., & Ramalho‐Santos, M. (2023) · Cell Reports · doi:10.1016/j.celrep.2022.111978 · Cited by 31
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Metadata
- Authors
- Bulut-Karslioglu, A., Biechele, S., Jin, H., Macrae, T. A., Hejna, M., Gertsenstein, M., Song, J. S., & Ramalho-Santos, M.
- Affiliations
- University of California, San Francisco (US)
- University of Illinois Urbana-Champaign (US)
- Toronto Centre for Phenogenomics (CA)
- Venue
- Nature
- Published
- 2016-11-23
- Volume
- 540
- Issue
- 7631
- Pages
- 119-123
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5143278
- OpenAlex
- W2553053943
- Cited by
- 283
- References
- 39
- Citations by year
- 2026: 17 · 2025: 40 · 2024: 37 · 2023: 32 · 2022: 32 · 2021: 42 · 2020: 23 · 2019: 27 · 2018: 17 · 2017: 14 · 2016: 2
- FWCI
- 10.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation
- National Institutes of Health (R01OD012204)
- University of California, San Francisco
- National Cancer Institute (P30CA082103, R01CA163336)
- National Institute of General Medical Sciences (R01GM113014)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063720)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- mTOR inhibition, delayed implantation, blastocyst development, pluripotency, epiblast, embryonic stem cells, long-term culture, transcriptional repression, histone modifications, peri-implantation development, developmental timing, assisted reproduction, regenerative medicine, rapamycin, mouse embryo, translational regulation, nutrient sensing
- MeSH terms
- Mouse Embryonic Stem Cells, Animals, Blastocyst, Cells, Cultured, Female, Germ Layers, Histones, Male, Transcription, Genetic, Protein Biosynthesis, Down-Regulation, Pluripotent Stem Cells, Embryonic Development, Mice, TOR Serine-Threonine Kinases, In Vitro Techniques
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