KEGG   PATHWAY: ko04550
ko04550                     Pathway                                

Signaling pathways regulating pluripotency of stem cells
Pluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date include embryonic stem (ES) and induced pluripotent stem (iPS) cells. ES cells are derived from the inner cell mass (ICM) of blastocyst-stage embryos. iPS cells are generated by reprogramming somatic cells back to pluripotent state with defined reprogramming factors, Oct4, Sox2, Klf4 and c-Myc (also known as Yamanaka factors). PSCs including ES cells and iPS cells are categorized into two groups by their morphology, gene expression profile and external signal dependence. Conventional mouse-type ES/iPS cells are called 'naive state' cells. They are mainly maintained under the control of LIF and BMP signaling. On the other hand, human-type ES/iPS cells, which are in need of Activin and FGF signaling, are termed 'primed state'. However, these signaling pathways converge towards the activation of a core transcriptional network that is similar in both groups and involves OCt4, Nanog and Sox2. The three transcription factors and their downstream target genes coordinately promote self-renewal and pluripotency.
Cellular Processes; Cellular community - eukaryotes
Pathway map
ko04550  Signaling pathways regulating pluripotency of stem cells

H01481  Myelodysplastic syndrome
H02151  Hereditary congenital facial paresis
H02295  Adermatoglyphia
H02296  Basan syndrome
Other DBs
GO: 2000036
K05419  leukemia inhibitory factor
K05058  leukemia inhibitory factor receptor
K05060  interleukin 6 signal transducer
K11217  Janus kinase 1 [EC:]
K04447  Janus kinase 2 [EC:]
K11218  Janus kinase 3 [EC:]
K04692  signal transducer and activator of transcription 3
K17846  krueppel-like factor 4
K16796  transcription factor SOX2 (SOX group B)
K04377  Myc proto-oncogene protein
K04364  growth factor receptor-bound protein 2
K04368  mitogen-activated protein kinase kinase 1 [EC:]
K04369  mitogen-activated protein kinase kinase 2 [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:]
K10177  T-box protein 3
K10164  homeobox protein Nanog
K04667  inhibin beta A chain
K22687  inhibin beta B chain
K22688  inhibin beta C chain
K22689  inhibin beta E chain
K04666  nodal
K13567  activin receptor type-1B [EC:]
K13568  activin receptor type-1C [EC:]
K04670  activin receptor type-2A [EC:]
K13596  activin receptor type-2B [EC:]
K04500  mothers against decapentaplegic homolog 2
K23605  mothers against decapentaplegic homolog 3
K04662  bone morphogenetic protein 4
K04673  bone morphogenetic protein receptor type-1A [EC:]
K13578  bone morphogenetic protein receptor type-1B [EC:]
K04675  activin receptor type-1 [EC:]
K04671  bone morphogenetic protein receptor type-2 [EC:]
K04676  mothers against decapentaplegic homolog 1
K16790  mothers against decapentaplegic homolog 5
K16791  mothers against decapentaplegic homolog 9
K04501  mothers against decapentaplegic homolog 4
K04680  DNA-binding protein inhibitor ID1
K17693  DNA-binding protein inhibitor ID2
K17694  DNA-binding protein inhibitor ID3
K17695  DNA-binding protein inhibitor ID4
K18498  dual specificity phosphatase 9 [EC:]
K04441  p38 MAP kinase [EC:]
K03209  wingless-type MMTV integration site family, member 1
K00182  wingless-type MMTV integration site family, member 2
K00312  wingless-type MMTV integration site family, member 3
K00408  wingless-type MMTV integration site family, member 4
K00444  wingless-type MMTV integration site family, member 5
K00445  wingless-type MMTV integration site family, member 6
K00572  wingless-type MMTV integration site family, member 7
K00714  wingless-type MMTV integration site family, member 8
K01064  wingless-type MMTV integration site family, member 9
K01357  wingless-type MMTV integration site family, member 10
K01384  wingless-type MMTV integration site family, member 11
K01558  wingless-type MMTV integration site family, member 16
K02432  frizzled 1/7
K02235  frizzled 2
K02329  frizzled 3
K02354  frizzled 4
K02375  frizzled 5/8
K02376  frizzled 6
K02842  frizzled 9/10
K02353  segment polarity protein dishevelled
K03083  glycogen synthase kinase 3 beta [EC:]
K02157  axin 1
K04385  axin 2
K02085  adenomatosis polyposis coli protein
K02105  catenin beta 1
K09063  transcription factor E2-alpha
K08553  estrogen-related receptor beta
K02620  transcription factor 7
K09367  POU domain transcription factor, class 5
K18497  fibroblast growth factor 2
K04362  fibroblast growth factor receptor 1 [EC:]
K05093  fibroblast growth factor receptor 2 [EC:]
K05094  fibroblast growth factor receptor 3 [EC:]
K05095  fibroblast growth factor receptor 4 [EC:]
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:]
K05459  insulin-like growth factor 1
K05087  insulin-like growth factor 1 receptor [EC:]
K09354  homeobox protein expressed in ES cells 1
K18487  zinc finger protein ZIC 3
K04668  left-right determination factor
K18499  Ski-like protein
K14439  SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 [EC:]
K11305  histone acetyltransferase MYST3 [EC:]
K11421  [histone H3]-N6,N6-dimethyl-lysine9 N-methyltransferase [EC:]
K11478  protein Jumonji
K09222  RE1-silencing transcription factor
K11138  telomere-associated protein RIF1
K11487  polycomb group RING finger protein 1
K11460  polycomb group RING finger protein 2
K11488  polycomb group RING finger protein 3
K11459  polycomb group RING finger protein 4
K11489  polycomb group RING finger protein 5
K11470  polycomb group RING finger protein 6
K08031  paired box protein 6
K15613  homeobox protein Meis1
K09301  homeobox protein HoxA/B/D1
K18493  LIM homeobox protein 5
K09326  homeobox protein OTX1
K09081  neurogenin 1
K09071  heart-and neural crest derivatives-expressed protein 1
K18489  homeobox protein DLX5
K18484  myogenic factor 5
K08026  one cut domain, family member 1 (hepatocyte nuclear factor 6)
K09370  insulin gene enhancer protein ISL-1
K09378  AT-binding transcription factor 1
K18491  homeobox protein ESX1
Bhartiya D, Lenka N (ed).
Pluripotent Stem Cells
InTech (2013)
Hassani SN, Totonchi M, Gourabi H, Scholer HR, Baharvand H
Signaling roadmap modulating naive and primed pluripotency.
Stem Cells Dev 23:193-208 (2014)
Jaenisch R, Young R
Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming.
Cell 132:567-82 (2008)
Zhang H, Wang ZZ
Mechanisms that mediate stem cell self-renewal and differentiation.
J Cell Biochem 103:709-18 (2008)
Itoh F, Watabe T, Miyazono K
Roles of TGF-beta family signals in the fate determination of pluripotent stem cells.
Semin Cell Dev Biol 32C:98-106 (2014)
Saunders A, Faiola F, Wang J
Concise review: pursuing self-renewal and pluripotency with the stem cell factor Nanog.
Stem Cells 31:1227-36 (2013)
Kuijk EW, Chuva de Sousa Lopes SM, Geijsen N, Macklon N, Roelen BA
The different shades of mammalian pluripotent stem cells.
Hum Reprod Update 17:254-71 (2011)
Okita K, Yamanaka S
Intracellular signaling pathways regulating pluripotency of embryonic stem cells.
Curr Stem Cell Res Ther 1:103-11 (2006)
Niwa H, Ogawa K, Shimosato D, Adachi K
A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells.
Nature 460:118-22 (2009)
Nakai-Futatsugi Y, Niwa H
Transcription factor network in embryonic stem cells: heterogeneity under the stringency.
Biol Pharm Bull 36:166-70 (2013)
Medvedev SP, Shevchenko AI, Zakian SM
Molecular basis of Mammalian embryonic stem cell pluripotency and self-renewal.
Acta Naturae 2:30-46 (2010)
Scheper W, Copray S
The molecular mechanism of induced pluripotency: a two-stage switch.
Stem Cell Rev 5:204-23 (2009)
Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA
Core transcriptional regulatory circuitry in human embryonic stem cells.
Cell 122:947-56 (2005)
Wang L, Miao YL, Zheng X, Lackford B, Zhou B, Han L, Yao C, Ward JM, Burkholder A, Lipchina I, Fargo DC, Hochedlinger K, Shi Y, Williams CJ, Hu G
The THO complex regulates pluripotency gene mRNA export and controls embryonic stem cell self-renewal and somatic cell reprogramming.
Cell Stem Cell 13:676-90 (2013)
Hasegawa Y, Tang D, Takahashi N, Hayashizaki Y, Forrest AR, Suzuki H
CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes.
Sci Rep 4:5228 (2014)
Sui L, Bouwens L, Mfopou JK
Signaling pathways during maintenance and definitive endoderm differentiation of embryonic stem cells.
Int J Dev Biol 57:1-12 (2013)
Do JT, Scholer HR
Regulatory circuits underlying pluripotency and reprogramming.
Trends Pharmacol Sci 30:296-302 (2009)
Pan G, Thomson JA
Nanog and transcriptional networks in embryonic stem cell pluripotency.
Cell Res 17:42-9 (2007)
Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lee CW, Zhao XD, Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL, Ruan Y, Lim B, Ng HH
The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.
Nat Genet 38:431-40 (2006)
Loh YH, Ng JH, Ng HH
Molecular framework underlying pluripotency.
Cell Cycle 7:885-91 (2008)
Greenow K, Clarke AR
Controlling the stem cell compartment and regeneration in vivo: the role of pluripotency pathways.
Physiol Rev 92:75-99 (2012)
ko04010  MAPK signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04310  Wnt signaling pathway
ko04350  TGF-beta signaling pathway
ko04630  JAK-STAT signaling pathway

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