ESC pluripotency pathways (WP339)

Mus musculus

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


Kristina Hanspers , Alex Pico , Cannin , Martijn Van Iersel , Egon Willighagen , Elisa Cirillo , Denise Slenter , Marvin Martens , Liyou an , and Eric Weitz


last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.


Mus musculus



Pathway Ontology

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

Cell Type Ontology

embryonic stem cell


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 C
Type your comment here
PIP3 Metabolite hmdb:HMDB0004249
GTP Metabolite hmdb:HMDB0001440
Fzd6 GeneProduct ncbigene:14368
Akt3 GeneProduct ncbigene:23797
Dvl3 GeneProduct ncbigene:13544
actr2 GeneProduct ncbigene:66713
Smad1 GeneProduct ncbigene:17125
Gsk3b GeneProduct ncbigene:56637
Smad5 GeneProduct ncbigene:17129
Myc GeneProduct ncbigene:17869
Ras GeneProduct ncbigene:15461
Bmpr1a GeneProduct ncbigene:12166
Braf GeneProduct ncbigene:109880
Pdgfa GeneProduct ncbigene:18590
Wnt3 GeneProduct ncbigene:22415
Fgf1 GeneProduct ncbigene:14164
Smad7 GeneProduct ncbigene:17131
Wnt5b GeneProduct ncbigene:22419
Fgf16 GeneProduct ncbigene:80903
Pdgfb GeneProduct ncbigene:18591
Fgf6 GeneProduct ncbigene:14177
Fgf15 GeneProduct ncbigene:14170
Acvr1 GeneProduct ncbigene:11477
Fgfr1 GeneProduct ncbigene:14182
Map2k1 GeneProduct ncbigene:26395
Ctnnb1 GeneProduct ncbigene:12387
Fzd4 GeneProduct ncbigene:14366
Fgf22 GeneProduct ncbigene:67112
Dvl1 GeneProduct ncbigene:13542
Jak1 GeneProduct ncbigene:16451
Bmpr2 GeneProduct ncbigene:12168
c-Jun GeneProduct ncbigene:16476
Fgf10 GeneProduct ncbigene:14165
Pik3cd GeneProduct ncbigene:18707
Fgf9 GeneProduct ncbigene:14180
Fzd8 GeneProduct ncbigene:14370
Stat3 GeneProduct ncbigene:20848
Sos1 GeneProduct ncbigene:20662
Fgf20 GeneProduct ncbigene:80857
Akt2 GeneProduct ncbigene:11652
Raf1 GeneProduct ncbigene:110157
Fgf11 GeneProduct ncbigene:14166
Wnt7a GeneProduct ncbigene:22421
Fzd9 GeneProduct ncbigene:14371
Smad1 GeneProduct ncbigene:17125
Il6st GeneProduct ncbigene:16195
Fgfr3 GeneProduct ncbigene:14184
Wnt5a GeneProduct ncbigene:22418
Mapk7 GeneProduct ncbigene:23939
Fzd2 GeneProduct ncbigene:57265
Fgf17 GeneProduct ncbigene:14171
Smad5 GeneProduct ncbigene:17129
Fzd5 GeneProduct ncbigene:14367
Wnt16 GeneProduct ncbigene:93735
Fgf18 GeneProduct ncbigene:14172
Fzd7 GeneProduct ncbigene:14369
Fzd1 GeneProduct ncbigene:14362
Egfr GeneProduct ncbigene:13649
Mdm2 GeneProduct ncbigene:17246
Wnt10a GeneProduct ncbigene:22409
Fgfr4 GeneProduct ncbigene:14186
Fgfr2 GeneProduct ncbigene:14183
Pdgfra GeneProduct ncbigene:18595
Mapk1 GeneProduct ncbigene:26413
Smad5 GeneProduct ncbigene:17129
Nog GeneProduct ncbigene:18121
Araf GeneProduct ncbigene:11836
Mtor GeneProduct ncbigene:56717
Smad4 GeneProduct ncbigene:17128
Stat3 GeneProduct ncbigene:20848
Wnt7b GeneProduct ncbigene:22422
Smad9 GeneProduct ncbigene:55994
Map2k3 GeneProduct ncbigene:26397
Sepp1 GeneProduct ncbigene:20363
Lif GeneProduct ncbigene:16878
Lifr GeneProduct ncbigene:16880
Wnt2 GeneProduct ncbigene:22413
Map2k5 GeneProduct ncbigene:23938
Pik3r2 GeneProduct ncbigene:18709
Smad1 GeneProduct ncbigene:17125
Lrp5 GeneProduct ncbigene:16973
Wnt9b GeneProduct ncbigene:22412
Axin1 GeneProduct ncbigene:12005
Elk GeneProduct ncbigene:13712
Fgf14 GeneProduct ncbigene:14169
Wnt3a GeneProduct ncbigene:22416
Bmpr1b GeneProduct ncbigene:12167
Mapk6 GeneProduct ncbigene:50772
Smad9 GeneProduct ncbigene:55994
SHP2 GeneProduct ncbigene:19247
Ctnnb1 GeneProduct ncbigene:12387
Fgf23 GeneProduct ncbigene:64654
Fgf5 GeneProduct ncbigene:14176
Gab1 GeneProduct ncbigene:14388
Pten GeneProduct ncbigene:19211
Wnt11 GeneProduct ncbigene:22411
Stat3 GeneProduct ncbigene:20848
Grb2 GeneProduct ncbigene:14784
Dvl2 GeneProduct ncbigene:13543
Apc GeneProduct ncbigene:11789
Akt1 GeneProduct ncbigene:11651
Tcf1 GeneProduct ncbigene:21405
Wnt4 GeneProduct ncbigene:22417
Smad6 GeneProduct ncbigene:17130
Fgf2 GeneProduct ncbigene:14173
Wnt1 GeneProduct ncbigene:22408
Mapk4 GeneProduct ncbigene:225724
Ctnnb1 GeneProduct ncbigene:12387
Fgf12 GeneProduct ncbigene:14167
Fgf21 GeneProduct ncbigene:56636
Wnt6 GeneProduct ncbigene:22420
Egf GeneProduct ncbigene:13645
Mapk12 GeneProduct ncbigene:29857
Fzd3 GeneProduct ncbigene:14365
Wnt10b GeneProduct ncbigene:22410
Pdgfrb GeneProduct ncbigene:18596
c-Fos GeneProduct ncbigene:14281
Fgf3 GeneProduct ncbigene:14174
Fgf13 GeneProduct ncbigene:14168
Smad9 GeneProduct ncbigene:55994
Map2k6 GeneProduct ncbigene:26399
Map2k2 GeneProduct ncbigene:26396
Fgf7 GeneProduct ncbigene:14178
Bmp4 GeneProduct ncbigene:12159
Fgf8 GeneProduct ncbigene:14179
Stat3 GeneProduct ncbigene:20848
Eras GeneProduct ncbigene:353283
Fgf4 GeneProduct ncbigene:14175
Wnt2b GeneProduct ncbigene:22414
Lrp6 GeneProduct ncbigene:16974
Smad4 GeneProduct ncbigene:17128
Smad1 GeneProduct ncbigene:17125
Smad5 GeneProduct ncbigene:17129
Smad9 GeneProduct ncbigene:55994
Smad4 GeneProduct ncbigene:17128
Stat3 GeneProduct ncbigene:20848
Stat3 GeneProduct ncbigene:20848
SHP2 GeneProduct ncbigene:19247
Jak1 GeneProduct ncbigene:16451
Ras GeneProduct ncbigene:15461
IKK Protein uniprot:O88351


  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