ESC Pluripotency Pathways (Mus musculus)

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2PPshophorylatedJNK-pSelf-renewalLIF SignalingRas/ERK pathwayBindingFrizzled ligandsBMP signalingR-Smad / Co-Smad complexSelf-renewalPKCG12 SignalingInhibits self-renewal (promotes differentiation)Wnt signalingPromotes self-renewal (inhibits differentiation)GPCR-Arrestin Signalsnon-canonical pathway-p DephosphorylationDegradation of beta-cateninPDESelf-renewalGi SignalingPI3 Kinase / Akt signalingNucleusSelf-renewalIl6stDvl2Mapk6NogCtnnb1SHP2Fgfr2Fgf13ElkRasMtorSmad6GDPFzd1Fzd6Fzd5Wnt7bDorsomorphinGsk3bSmad5Fgf16PdgfbPik3r2Bmpr1bStat3Fgf18Mapk7Smad5Smad1EgfrLifrWnt1Axin1Dvl3Sepp1Wnt5aFgfr4c-JunWnt9bLifMapk12Fgf4Stat3Pik3cdMapk1PtenArafFzd9Smad7Wnt7aLrp5MycCtnnb1Wnt4PdgfaWnt3Smad5Wnt3aGTPWnt10aMap2k2Tcf1Fgf9Fgf7Fgf10Smad1PdgfraSmad9PdgfrbCtnnb1actr2Fzd7PIP2Fzd2Smad9Bmpr1aFgf5Smad4Smad1BrafWnt16Map2k1Stat3Fgf20Bmp4Dvl1Akt1Fgf17Grb2Bmpr2ErasFzd4Wnt6Fgf15Lrp6Ca2+PIP2Wnt2bFgf23Map2k5Fgf3Wnt10bFgf2Akt2Sos1Fgf22Akt3Stat3Fgf8c-FosFgfr3Fgf12EgfRaf1Map2k3ApcWnt5bFzd8PIP3Acvr1Fzd3Fgfr1Fgf11Wnt11IKKFgf14Mapk4Mdm2Fgf1Fgf21Map2k6Wnt2Smad9actr2bFgf6Jak1Gab1PPSmad41, 3PPPPPPPPPPP4Smad1Smad5Smad9Smad4Stat3Stat3PSHP2Jak1Ras


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

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Ontology Terms



  1. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE; ''Role of AMP-activated protein kinase in mechanism of metformin action.''; J Clin Invest, 2001 PubMed Europe PMC Scholia
  2. Okita K, Yamanaka S; ''Intracellular signaling pathways regulating pluripotency of embryonic stem cells.''; Curr Stem Cell Res Ther, 2006 PubMed Europe PMC Scholia
  3. Hao J, Daleo MA, Murphy CK, Yu PB, Ho JN, Hu J, Peterson RT, Hatzopoulos AK, Hong CC; ''Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells.''; PLoS ONE, 2008 PubMed Europe PMC Scholia
  4. Yuasa S, Itabashi Y, Koshimizu U, Tanaka T, Sugimura K, Kinoshita M, Hattori F, Fukami S, Shimazaki T, Ogawa S, Okano H, Fukuda K; ''Transient inhibition of BMP signaling by Noggin induces cardiomyocyte differentiation of mouse embryonic stem cells.''; Nat Biotechnol, 2005 PubMed Europe PMC Scholia


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108619view16:05, 12 January 2020LiyouModified title
106879view13:35, 17 September 2019MaintBotHMDB identifier normalization
94309view11:55, 1 September 2017Marvin M2Changed an arrow and connected the last unconnected line
94211view21:25, 25 August 2017DeSlAdded ID for PIP2
91004view13:16, 20 December 2016ElisaFixed unconnected lines
90948view04:00, 19 December 2016Khanspersupdated description
79831view09:15, 17 April 2015EgonwReplaced a gene name by its Entrez gene ID.
79829view09:11, 17 April 2015EgonwAdded an @chebit identifier for dorsomorphin.
78417view10:25, 7 January 2015MaintBotadded missing graphIds
77160view21:05, 29 July 2014KhanspersOntology Term : 'the extracellular signal-regulated Raf/Mek/Erk signaling pathway' added !
77159view21:04, 29 July 2014KhanspersOntology Term : 'embryonic stem cell' added !
76807view18:29, 16 July 2014Khanspersreplaced interactions with graphical lines in legend
74899view23:50, 7 May 2014Khanspersadded xrefs, fixed interactions
74898view22:36, 7 May 2014Khanspersstates, arrow types, layout
71750view20:20, 17 October 2013MaintBotAutomated update of data sources
70844view23:43, 11 September 2013Khanspersadded state
70843view23:40, 11 September 2013KhanspersAdded
69182view18:21, 8 July 2013MaintBotUpdated to 2013 gpml schema
42897view12:10, 19 May 2011MartijnVanIerselchange conflicting id
41371view00:28, 2 March 2011MaintBotRemoved redundant pathway information and comments
34812view00:46, 21 January 2010KhanspersRemoved rectangles
34811view00:44, 21 January 2010KhanspersAdded reference
34810view00:42, 21 January 2010KhanspersModified description
34417view23:14, 9 December 2009MaintBotAutomatic update of empty xrefs
33694view23:14, 3 December 2009KhanspersAdded connectors
33693view23:03, 3 December 2009KhanspersPeriodical save, work in progress
33692view22:53, 3 December 2009KhanspersPeriodical save, work in progress
33691view22:43, 3 December 2009KhanspersPeriodical save, work in progress
32056view13:32, 14 August 2009MaintBotFixed group labels
28128view19:39, 27 January 2009KhanspersChanged name
28115view00:33, 27 January 2009AlexanderPicoReverted to version '17:30, 26 January 2009' by AlexanderPico
28114view00:31, 27 January 2009AlexanderPicotesting reference count
28113view00:30, 27 January 2009AlexanderPicofixed legend
28111view00:11, 27 January 2009AlexanderPicotesting reference counts
28090view19:35, 23 January 2009AlexanderPicotesting reference counts
26504view19:25, 5 December 2008Canninmoved by accident
26502view19:23, 5 December 2008CanninPeriodical save, work in progress
21391view11:31, 14 November 2008MaintBot[[Pathway:Mus musculus:ESC Pluripotency Pathways]] moved to [[Pathway:WP339]]: Moved to stable identifier
18186view01:46, 9 August 2008AlexanderPicoadded comment to dorsomorphin
18184view01:44, 9 August 2008AlexanderPicoAdded BMP pathway inhibitors, Nog and Dorsomorphin
8014view13:46, 7 January 2008MaintBot[[Pathway:Mouse:ESC Pluripotency Pathways]] moved to [[Pathway:Mus musculus:ESC Pluripotency Pathways]]: Renaming species
7630view16:06, 18 December 2007MaintBotfixed category names
7218view12:41, 4 November 2007MaintBotAdded categories to GPML
6433view22:18, 22 May 2007Khanspersgpml file for [[Mouse:ESC_Pluripotency_Pathways]]

External references


View all...
NameTypeDatabase referenceComment
Acvr1GeneProduct11477 (Entrez Gene)
Akt1GeneProduct11651 (Entrez Gene)
Akt2GeneProduct11652 (Entrez Gene)
Akt3GeneProduct23797 (Entrez Gene)
ApcGeneProduct11789 (Entrez Gene)
ArafGeneProduct11836 (Entrez Gene)
Axin1GeneProduct12005 (Entrez Gene)
Bmp4GeneProduct12159 (Entrez Gene)
Bmpr1aGeneProduct12166 (Entrez Gene)
Bmpr1bGeneProduct12167 (Entrez Gene)
Bmpr2GeneProduct12168 (Entrez Gene)
BrafGeneProduct109880 (Entrez Gene)
Ca2+MetaboliteHMDB0000464 (HMDB)
Ctnnb1GeneProduct12387 (Entrez Gene)
DorsomorphinMetaboliteCHEBI:78510 (ChEBI)
  • Also known as Compound C
  • Type your comment here
Dvl1GeneProduct13542 (Entrez Gene)
Dvl2GeneProduct13543 (Entrez Gene)
Dvl3GeneProduct13544 (Entrez Gene)
EgfGeneProduct13645 (Entrez Gene)
EgfrGeneProduct13649 (Entrez Gene)
ElkGeneProduct13712 (Entrez Gene)
ErasGeneProduct353283 (Entrez Gene)
Fgf10GeneProduct14165 (Entrez Gene)
Fgf11GeneProduct14166 (Entrez Gene)
Fgf1GeneProduct14164 (Entrez Gene)
Fgf12GeneProduct14167 (Entrez Gene)
Fgf13GeneProduct14168 (Entrez Gene)
Fgf14GeneProduct14169 (Entrez Gene)
Fgf15GeneProduct14170 (Entrez Gene)
Fgf16GeneProduct80903 (Entrez Gene)
Fgf17GeneProduct14171 (Entrez Gene)
Fgf18GeneProduct14172 (Entrez Gene)
Fgf20GeneProduct80857 (Entrez Gene)
Fgf2GeneProduct14173 (Entrez Gene)
Fgf21GeneProduct56636 (Entrez Gene)
Fgf22GeneProduct67112 (Entrez Gene)
Fgf23GeneProduct64654 (Entrez Gene)
Fgf3GeneProduct14174 (Entrez Gene)
Fgf4GeneProduct14175 (Entrez Gene)
Fgf5GeneProduct14176 (Entrez Gene)
Fgf6GeneProduct14177 (Entrez Gene)
Fgf7GeneProduct14178 (Entrez Gene)
Fgf8GeneProduct14179 (Entrez Gene)
Fgf9GeneProduct14180 (Entrez Gene)
Fgfr1GeneProduct14182 (Entrez Gene)
Fgfr2GeneProduct14183 (Entrez Gene)
Fgfr3GeneProduct14184 (Entrez Gene)
Fgfr4GeneProduct14186 (Entrez Gene)
Fzd1GeneProduct14362 (Entrez Gene)
Fzd2GeneProduct57265 (Entrez Gene)
Fzd3GeneProduct14365 (Entrez Gene)
Fzd4GeneProduct14366 (Entrez Gene)
Fzd5GeneProduct14367 (Entrez Gene)
Fzd6GeneProduct14368 (Entrez Gene)
Fzd7GeneProduct14369 (Entrez Gene)
Fzd8GeneProduct14370 (Entrez Gene)
Fzd9GeneProduct14371 (Entrez Gene)
GDPMetaboliteHMDB0000960 (HMDB)
GTPMetaboliteHMDB0001440 (HMDB)
Gab1GeneProduct14388 (Entrez Gene)
Grb2GeneProduct14784 (Entrez Gene)
Gsk3bGeneProduct56637 (Entrez Gene)
IKKProteinO88351 (Uniprot-TrEMBL)
Il6stGeneProduct16195 (Entrez Gene)
Jak1GeneProduct16451 (Entrez Gene)
LifGeneProduct16878 (Entrez Gene)
LifrGeneProduct16880 (Entrez Gene)
Lrp5GeneProduct16973 (Entrez Gene)
Lrp6GeneProduct16974 (Entrez Gene)
Map2k1GeneProduct26395 (Entrez Gene)
Map2k2GeneProduct26396 (Entrez Gene)
Map2k3GeneProduct26397 (Entrez Gene)
Map2k5GeneProduct23938 (Entrez Gene)
Map2k6GeneProduct26399 (Entrez Gene)
Mapk12GeneProduct29857 (Entrez Gene)
Mapk1GeneProduct26413 (Entrez Gene)
Mapk4GeneProduct225724 (Entrez Gene)
Mapk6GeneProduct50772 (Entrez Gene)
Mapk7GeneProduct23939 (Entrez Gene)
Mdm2GeneProduct17246 (Entrez Gene)
MtorGeneProduct56717 (Entrez Gene)
MycGeneProduct17869 (Entrez Gene)
NogGeneProduct18121 (Entrez Gene)
PIP2MetaboliteQ27088398 (Wikidata)
PIP3MetaboliteHMDB0004249 (HMDB)
PdgfaGeneProduct18590 (Entrez Gene)
PdgfbGeneProduct18591 (Entrez Gene)
PdgfraGeneProduct18595 (Entrez Gene)
PdgfrbGeneProduct18596 (Entrez Gene)
Pik3cdGeneProduct18707 (Entrez Gene)
Pik3r2GeneProduct18709 (Entrez Gene)
PtenGeneProduct19211 (Entrez Gene)
Raf1GeneProduct110157 (Entrez Gene)
RasGeneProduct15461 (Entrez Gene)
SHP2GeneProduct19247 (Entrez Gene)
Sepp1GeneProduct20363 (Entrez Gene)
Smad1GeneProduct17125 (Entrez Gene)
Smad4GeneProduct17128 (Entrez Gene)
Smad5GeneProduct17129 (Entrez Gene)
Smad6GeneProduct17130 (Entrez Gene)
Smad7GeneProduct17131 (Entrez Gene)
Smad9GeneProduct55994 (Entrez Gene)
Sos1GeneProduct20662 (Entrez Gene)
Stat3GeneProduct20848 (Entrez Gene)
Tcf1GeneProduct21405 (Entrez Gene)
Wnt10aGeneProduct22409 (Entrez Gene)
Wnt10bGeneProduct22410 (Entrez Gene)
Wnt11GeneProduct22411 (Entrez Gene)
Wnt1GeneProduct22408 (Entrez Gene)
Wnt16GeneProduct93735 (Entrez Gene)
Wnt2GeneProduct22413 (Entrez Gene)
Wnt2bGeneProduct22414 (Entrez Gene)
Wnt3GeneProduct22415 (Entrez Gene)
Wnt3aGeneProduct22416 (Entrez Gene)
Wnt4GeneProduct22417 (Entrez Gene)
Wnt5aGeneProduct22418 (Entrez Gene)
Wnt5bGeneProduct22419 (Entrez Gene)
Wnt6GeneProduct22420 (Entrez Gene)
Wnt7aGeneProduct22421 (Entrez Gene)
Wnt7bGeneProduct22422 (Entrez Gene)
Wnt9bGeneProduct22412 (Entrez Gene)
actr2GeneProduct66713 (Entrez Gene)
c-FosGeneProduct14281 (Entrez Gene)
c-JunGeneProduct16476 (Entrez Gene)

Annotated Interactions

No annotated interactions

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