Embryonic stem cell pluripotency pathways (WP3931)
Homo sapiens
The cytokine LIF and its downstream effector STAT3 are essential for maintenance of pluripotency in mouse ES cells. The requirement for the transcription factor Oct3/4 for ES cell pluripotency is also well-documented. However, LIF is not involved in self-renewal of human ES cells, suggesting that other pathways must play an important role in this process. The importance of other signal transduction pathways, including BMP and Wnt signalings, as well as novel transcription factors such as Nanog, is now being recognized. Pathway source: Intracellular Signaling Pathways Regulating Pluripotency of Embryonic Stem Cells, Okita et al, Current Stem Cell Research and Therapy, 2006, 1, 103-111. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3931 CPTAC Assay Portal]
Authors
Kristina Hanspers , Elisa Cirillo , Denise Slenter , Marvin Martens , and Eric WeitzActivity
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Cited In
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Organisms
Homo sapiensCommunities
Annotations
Cell Type Ontology
embryonic stem cell embryonic stem cellPathway Ontology
the extracellular signal-regulated Raf/Mek/Erk signaling pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| Ca2+ | Metabolite | hmdb:HMDB0000464 | |
| PIP2 | Metabolite | wikidata:Q27088398 | |
| PIP2 | Metabolite | wikidata:Q27088398 | |
| GDP | Metabolite | hmdb:HMDB0000960 | |
| Dorsomorphin | Metabolite | chebi:78510 | Also known as Compound CType your comment here |
| PIP3 | Metabolite | hmdb:HMDB0004249 | |
| GTP | Metabolite | hmdb:HMDB0001440 | |
| FZD6 | GeneProduct | ensembl:ENSG00000164930 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14368 |
| AKT3 | GeneProduct | ensembl:ENSG00000117020 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:23797 |
| DVL3 | GeneProduct | ensembl:ENSG00000161202 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13544 |
| ACTR2 | GeneProduct | ensembl:ENSG00000138071 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:66713 |
| SMAD1 | GeneProduct | ensembl:ENSG00000170365 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17125 |
| GSK3B | GeneProduct | ensembl:ENSG00000082701 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:56637 |
| SMAD5 | GeneProduct | ensembl:ENSG00000113658 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17129 |
| HRAS | GeneProduct | ensembl:ENSG00000174775 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:15461 |
| BMPR1A | GeneProduct | ensembl:ENSG00000107779 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12166 |
| BRAF | GeneProduct | ensembl:ENSG00000157764 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:109880 |
| PDGFA | GeneProduct | ensembl:ENSG00000197461 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18590 |
| WNT3 | GeneProduct | ensembl:ENSG00000108379 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22415 |
| FGF1 | GeneProduct | ensembl:ENSG00000113578 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14164 |
| SMAD7 | GeneProduct | ensembl:ENSG00000101665 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17131 |
| WNT5B | GeneProduct | ensembl:ENSG00000111186 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22419 |
| FGF16 | GeneProduct | ensembl:ENSG00000196468 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:80903 |
| PDGFB | GeneProduct | ensembl:ENSG00000100311 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18591 |
| FGF6 | GeneProduct | ensembl:ENSG00000111241 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14177 |
| FGF19 | GeneProduct | ensembl:ENSG00000162344 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14170 |
| ACVR1 | GeneProduct | ensembl:ENSG00000115170 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11477 |
| FGFR1 | GeneProduct | ensembl:ENSG00000077782 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14182 |
| MAP2K1 | GeneProduct | ensembl:ENSG00000169032 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:26395 |
| CTNNB1 | GeneProduct | ensembl:ENSG00000168036 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12387 |
| FZD4 | GeneProduct | ensembl:ENSG00000174804 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14366 |
| FGF22 | GeneProduct | ensembl:ENSG00000070388 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:67112 |
| DVL1 | GeneProduct | ensembl:ENSG00000107404 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13542 |
| JAK1 | GeneProduct | ensembl:ENSG00000162434 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16451 |
| BMPR2 | GeneProduct | ensembl:ENSG00000204217 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12168 |
| JUN | GeneProduct | ensembl:ENSG00000177606 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16476 |
| FGF10 | GeneProduct | ensembl:ENSG00000070193 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14165 |
| PIK3CD | GeneProduct | ensembl:ENSG00000171608 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18707 |
| FGF9 | GeneProduct | ensembl:ENSG00000102678 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14180 |
| FZD8 | GeneProduct | ensembl:ENSG00000177283 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14370 |
| STAT3 | GeneProduct | ensembl:ENSG00000168610 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20848 |
| SOS1 | GeneProduct | ensembl:ENSG00000115904 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20662 |
| FGF20 | GeneProduct | ensembl:ENSG00000078579 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:80857 |
| AKT2 | GeneProduct | ensembl:ENSG00000105221 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11652 |
| RAF1 | GeneProduct | ensembl:ENSG00000132155 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:110157 |
| FGF11 | GeneProduct | ensembl:ENSG00000161958 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14166 |
| WNT7A | GeneProduct | ensembl:ENSG00000154764 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22421 |
| FZD9 | GeneProduct | ensembl:ENSG00000188763 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14371 |
| SMAD1 | GeneProduct | ensembl:ENSG00000170365 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17125 |
| IL6ST | GeneProduct | ensembl:ENSG00000134352 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16195 |
| FGFR3 | GeneProduct | ensembl:ENSG00000068078 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14184 |
| WNT5A | GeneProduct | ensembl:ENSG00000114251 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22418 |
| MAPK7 | GeneProduct | ensembl:ENSG00000166484 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:23939 |
| FZD2 | GeneProduct | ensembl:ENSG00000180340 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:57265 |
| FGF17 | GeneProduct | ensembl:ENSG00000158815 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14171 |
| SMAD5 | GeneProduct | ensembl:ENSG00000113658 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17129 |
| FZD5 | GeneProduct | ensembl:ENSG00000163251 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14367 |
| WNT16 | GeneProduct | ensembl:ENSG00000002745 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:93735 |
| FGF18 | GeneProduct | ensembl:ENSG00000156427 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14172 |
| FZD7 | GeneProduct | ensembl:ENSG00000155760 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14369 |
| FZD1 | GeneProduct | ensembl:ENSG00000157240 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14362 |
| EGFR | GeneProduct | ensembl:ENSG00000146648 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13649 |
| MDM2 | GeneProduct | ensembl:ENSG00000135679 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17246 |
| WNT10A | GeneProduct | ensembl:ENSG00000135925 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22409 |
| FGFR4 | GeneProduct | ensembl:ENSG00000160867 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14186 |
| FGFR2 | GeneProduct | ensembl:ENSG00000066468 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14183 |
| PDGFRA | GeneProduct | ensembl:ENSG00000134853 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18595 |
| MAPK1 | GeneProduct | ensembl:ENSG00000100030 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:26413 |
| SMAD5 | GeneProduct | ensembl:ENSG00000113658 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17129 |
| NOG | GeneProduct | ensembl:ENSG00000183691 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18121 |
| ARAF | GeneProduct | ensembl:ENSG00000078061 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11836 |
| MTOR | GeneProduct | ensembl:ENSG00000198793 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:56717 |
| SMAD4 | GeneProduct | ensembl:ENSG00000141646 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17128 |
| STAT3 | GeneProduct | ensembl:ENSG00000168610 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20848 |
| WNT7B | GeneProduct | ensembl:ENSG00000188064 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22422 |
| SMAD9 | GeneProduct | ensembl:ENSG00000120693 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:55994 |
| MAP2K3 | GeneProduct | ensembl:ENSG00000034152 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:26397 |
| SELENOP | GeneProduct | ensembl:ENSG00000250722 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20363 |
| LIF | GeneProduct | ensembl:ENSG00000128342 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16878 |
| LIFR | GeneProduct | ensembl:ENSG00000113594 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16880 |
| WNT2 | GeneProduct | ensembl:ENSG00000105989 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22413 |
| MAP2K5 | GeneProduct | ensembl:ENSG00000137764 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:23938 |
| PIK3R2 | GeneProduct | ensembl:ENSG00000105647 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18709 |
| SMAD1 | GeneProduct | ensembl:ENSG00000170365 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17125 |
| LRP5 | GeneProduct | ensembl:ENSG00000162337 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16973 |
| WNT9B | GeneProduct | ensembl:ENSG00000158955 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22412 |
| AXIN1 | GeneProduct | ensembl:ENSG00000103126 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12005 |
| ELK1 | GeneProduct | ensembl:ENSG00000126767 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13712 |
| FGF14 | GeneProduct | ensembl:ENSG00000102466 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14169 |
| WNT3A | GeneProduct | ensembl:ENSG00000154342 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22416 |
| BMPR1B | GeneProduct | ensembl:ENSG00000138696 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12167 |
| MAPK6 | GeneProduct | ensembl:ENSG00000069956 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:50772 |
| SMAD9 | GeneProduct | ensembl:ENSG00000120693 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:55994 |
| PTPN11 | GeneProduct | ensembl:ENSG00000179295 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:19247 |
| CTNNB1 | GeneProduct | ensembl:ENSG00000168036 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12387 |
| FGF23 | GeneProduct | ensembl:ENSG00000118972 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:64654 |
| FGF5 | GeneProduct | ensembl:ENSG00000138675 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14176 |
| GAB1 | GeneProduct | ensembl:ENSG00000109458 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14388 |
| PTEN | GeneProduct | ensembl:ENSG00000171862 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:19211 |
| WNT11 | GeneProduct | ensembl:ENSG00000085741 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22411 |
| STAT3 | GeneProduct | ensembl:ENSG00000168610 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20848 |
| GRB2 | GeneProduct | ensembl:ENSG00000177885 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14784 |
| DVL2 | GeneProduct | ensembl:ENSG00000004975 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13543 |
| APC | GeneProduct | ensembl:ENSG00000134982 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11789 |
| AKT1 | GeneProduct | ensembl:ENSG00000142208 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11651 |
| HNF1A | GeneProduct | ensembl:ENSG00000135100 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:21405 |
| WNT4 | GeneProduct | ensembl:ENSG00000162552 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22417 |
| SMAD6 | GeneProduct | ensembl:ENSG00000137834 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17130 |
| FGF2 | GeneProduct | ensembl:ENSG00000138685 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14173 |
| WNT1 | GeneProduct | ensembl:ENSG00000125084 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22408 |
| MAPK4 | GeneProduct | ensembl:ENSG00000141639 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:225724 |
| CTNNB1 | GeneProduct | ensembl:ENSG00000168036 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12387 |
| FGF12 | GeneProduct | ensembl:ENSG00000114279 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14167 |
| FGF21 | GeneProduct | ensembl:ENSG00000105550 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:56636 |
| WNT6 | GeneProduct | ensembl:ENSG00000115596 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22420 |
| EGF | GeneProduct | ensembl:ENSG00000138798 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:13645 |
| MAPK12 | GeneProduct | ensembl:ENSG00000188130 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:29857 |
| FZD3 | GeneProduct | ensembl:ENSG00000104290 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14365 |
| WNT10B | GeneProduct | ensembl:ENSG00000169884 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22410 |
| PDGFRB | GeneProduct | ensembl:ENSG00000113721 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18596 |
| FOS | GeneProduct | ensembl:ENSG00000170345 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14281 |
| FGF3 | GeneProduct | ensembl:ENSG00000186895 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14174 |
| FGF13 | GeneProduct | ensembl:ENSG00000129682 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14168 |
| SMAD9 | GeneProduct | ensembl:ENSG00000120693 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:55994 |
| MAP2K6 | GeneProduct | ensembl:ENSG00000108984 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:26399 |
| MAP2K2 | GeneProduct | ensembl:ENSG00000126934 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:26396 |
| FGF7 | GeneProduct | ensembl:ENSG00000140285 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14178 |
| BMP4 | GeneProduct | ensembl:ENSG00000125378 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12159 |
| FGF8 | GeneProduct | ensembl:ENSG00000107831 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14179 |
| STAT3 | GeneProduct | ensembl:ENSG00000168610 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20848 |
| ERAS | GeneProduct | ensembl:ENSG00000187682 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:353283 |
| FGF4 | GeneProduct | ensembl:ENSG00000075388 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:14175 |
| WNT2B | GeneProduct | ensembl:ENSG00000134245 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:22414 |
| LRP6 | GeneProduct | ensembl:ENSG00000070018 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16974 |
| SMAD4 | GeneProduct | ensembl:ENSG00000141646 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17128 |
| SMAD1 | GeneProduct | ensembl:ENSG00000170365 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17125 |
| SMAD5 | GeneProduct | ensembl:ENSG00000113658 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17129 |
| SMAD9 | GeneProduct | ensembl:ENSG00000120693 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:55994 |
| SMAD4 | GeneProduct | ensembl:ENSG00000141646 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:17128 |
| STAT3 | GeneProduct | ensembl:ENSG00000168610 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20848 |
| STAT3 | GeneProduct | ensembl:ENSG00000168610 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:20848 |
| PTPN11 | GeneProduct | ensembl:ENSG00000179295 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:19247 |
| JAK1 | GeneProduct | ensembl:ENSG00000162434 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16451 |
| HRAS | GeneProduct | ensembl:ENSG00000174775 | Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:15461 |
References
- Role of AMP-activated protein kinase in mechanism of metformin action. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. J Clin Invest. 2001 Oct;108(8):1167–74. PubMed Europe PMC Scholia
- Transient inhibition of BMP signaling by Noggin induces cardiomyocyte differentiation of mouse embryonic stem cells. Yuasa S, Itabashi Y, Koshimizu U, Tanaka T, Sugimura K, Kinoshita M, et al. Nat Biotechnol. 2005 May;23(5):607–11. PubMed Europe PMC Scholia
- Intracellular signaling pathways regulating pluripotency of embryonic stem cells. Okita K, Yamanaka S. Curr Stem Cell Res Ther. 2006 Jan;1(1):103–11. PubMed Europe PMC Scholia
- Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells. Hao J, Daleo MA, Murphy CK, Yu PB, Ho JN, Hu J, et al. PLoS One. 2008 Aug 6;3(8):e2904. PubMed Europe PMC Scholia