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 , Eric Weitz , and Egon Willighagen

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Cell Type Ontology

embryonic stem cell embryonic stem cell

Pathway Ontology

the extracellular signal-regulated Raf/Mek/Erk signaling pathway

Participants

Label Type Compact URI Comment
Ca2+ Metabolite hmdb:HMDB0000464
PIP2 Metabolite wikidata:Q27088398
GDP Metabolite hmdb:HMDB0000960
Dorsomorphin Metabolite chebi:78510 Also known as Compound C
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
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
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
ACVR2B GeneProduct ncbigene:93
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
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
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
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
PTPN11 GeneProduct ensembl:ENSG00000179295 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:19247
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
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
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
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
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

References

  1. 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
  2. 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
  3. 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
  4. 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