KEGG   PATHWAY: gvr04550
Entry
gvr04550                    Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Galeopterus variegatus (Sunda flying lemur)
Description
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.
Class
Cellular Processes; Cellular community - eukaryotes
Pathway map
gvr04550  Signaling pathways regulating pluripotency of stem cells
gvr04550

Other DBs
GO: 2000036
Organism
Galeopterus variegatus (Sunda flying lemur) [GN:gvr]
Gene
103583293  [KO:K10177]
103583582  [KO:K18493]
103585172  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
103585225  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
103585422  RIF1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
103585463  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103585545  DLX5; homeobox protein DLX-5 [KO:K18489]
103586041  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
103586572  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103586698  FZD5; frizzled-5 [KO:K02375]
103586784  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103586841  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
103586890  HOXA1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
103587428  HOXB1; homeobox protein Hox-B1 [KO:K09301]
103587477  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
103587478  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
103587648  FGFR3; fibroblast growth factor receptor 3 [KO:K05094] [EC:2.7.10.1]
103587820  MYC; myc proto-oncogene protein [KO:K04377]
103587839  PCGF3; polycomb group RING finger protein 3 isoform X1 [KO:K11488]
103587883  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103587889  PAX6; paired box protein Pax-6 [KO:K08031]
103588371  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
103588444  BMP4; bone morphogenetic protein 4 [KO:K04662]
103588593  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
103588804  WNT8B; protein Wnt-8b [KO:K00714]
103588854  WNT1; proto-oncogene Wnt-1 [KO:K03209]
103588855  WNT10B; protein Wnt-10b [KO:K01357]
103589329  NRAS; GTPase NRas [KO:K07828]
103589384  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
103589407  LIF; leukemia inhibitory factor [KO:K05419]
103590234  WNT5B; protein Wnt-5b [KO:K00444]
103590279  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103590291  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
103590315  FZD4; frizzled-4 [KO:K02354]
103590371  LHX5; LIM/homeobox protein Lhx5 [KO:K18493]
103590450  WNT11; protein Wnt-11 [KO:K01384]
103590618  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
103590629  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
103590674  WNT7A; protein Wnt-7a [KO:K00572]
103590842  HAND1; heart- and neural crest derivatives-expressed protein 1 [KO:K09071]
103590950  OTX1; homeobox protein OTX1 [KO:K09326]
103591002  MEIS1; homeobox protein Meis1 isoform X1 [KO:K15613]
103591151  HOXD1; homeobox protein Hox-D1 [KO:K09301]
103591440  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
103591505  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
103592000  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
103592116  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
103592192  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103592399  TCF7; transcription factor 7 isoform X1 [KO:K02620]
103592626  ISL1; insulin gene enhancer protein ISL-1 [KO:K09370]
103592629  MYF5; myogenic factor 5 [KO:K18484]
103593101  FGFR4; fibroblast growth factor receptor 4 isoform X1 [KO:K05095] [EC:2.7.10.1]
103593202  SKIL; ski-like protein [KO:K18499]
103593677  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
103593683  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103593776  WNT2B; protein Wnt-2b [KO:K00182]
103593850  PCGF1; polycomb group RING finger protein 1 [KO:K11487]
103593898  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
103593930  DUSP9; dual specificity protein phosphatase 9 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
103594196  INHBC; inhibin beta C chain [KO:K22688]
103594197  INHBE; inhibin beta E chain [KO:K22689]
103594259  ESRRB; steroid hormone receptor ERR2 [KO:K08553]
103594538  ZIC3; zinc finger protein ZIC 3 isoform X1 [KO:K18487]
103594579  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
103594630  REST; RE1-silencing transcription factor [KO:K09222]
103594788  FZD6; frizzled-6 [KO:K02376]
103594841  PCGF6; polycomb group RING finger protein 6 isoform X1 [KO:K11470]
103594862  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
103595017  FZD2; frizzled-2 [KO:K02235]
103595205  SOX2; transcription factor SOX-2 [KO:K16796]
103595208  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
103595264  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
103595293  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
103595356  [KO:K04692]
103595392  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103595407  ZFHX3; zinc finger homeobox protein 3 isoform X1 [KO:K09378]
103596055  FZD1; frizzled-1 [KO:K02432]
103596129  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103596160  LIFR; leukemia inhibitory factor receptor [KO:K05058]
103596384  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103596654  FZD9; frizzled-9 [KO:K02842]
103596735  FZD10; frizzled-10 [KO:K02842]
103597028  PCGF2; polycomb group RING finger protein 2 isoform X1 [KO:K11460]
103597215  WNT2; protein Wnt-2 [KO:K00182]
103597246  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
103597396  HESX1; homeobox expressed in ES cells 1 isoform X1 [KO:K09354]
103597471  AXIN2; axin-2 isoform X1 [KO:K04385]
103597574  WNT3; proto-oncogene Wnt-3 [KO:K00312]
103597576  WNT9B; protein Wnt-9b [KO:K01064]
103597620  FZD7; LOW QUALITY PROTEIN: frizzled-7 [KO:K02432]
103597875  [KO:K14439] [EC:5.6.2.-]
103598228  [KO:K18491]
103598325  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103598517  SMAD5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
103598755  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
103598931  INHBA; inhibin beta A chain [KO:K04667]
103598980  [KO:K00408]
103599501  KRAS; GTPase KRas [KO:K07827]
103599555  KLF4; Krueppel-like factor 4 isoform X1 [KO:K17846]
103600109  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
103600118  LEFTY2; left-right determination factor 2 isoform X1 [KO:K04668]
103600120  [KO:K04668]
103600170  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
103600244  SETDB1; histone-lysine N-methyltransferase SETDB1 isoform X1 [KO:K11421] [EC:2.1.1.366]
103600246  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
103600247  WNT10A; protein Wnt-10a [KO:K01357]
103600324  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103600617  JARID2; protein Jumonji isoform X1 [KO:K11478]
103600945  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
103600951  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
103601073  NANOG; homeobox protein NANOG isoform X1 [KO:K10164]
103601242  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
103601524  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
103601552  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
103602056  NODAL; nodal homolog [KO:K04666]
103602527  INHBB; inhibin beta B chain [KO:K22687]
103602994  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
103603163  ONECUT1; hepatocyte nuclear factor 6 isoform X1 [KO:K08026]
103603315  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
103604077  FZD3; frizzled-3 [KO:K02329]
103604797  AXIN1; axin-1 isoform X1 [KO:K02157]
103605007  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
103605402  WNT8A; protein Wnt-8a [KO:K00714]
103605695  [KO:K00312]
103605697  WNT9A; protein Wnt-9a [KO:K01064]
103605698  [KO:K04456] [EC:2.7.11.1]
103606025  TCF3; transcription factor E2-alpha isoform X1 [KO:K09063]
103606649  POU5F1; POU domain, class 5, transcription factor 1 [KO:K09367]
103607428  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
103607442  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103607489  [KO:K01064]
103607780  [KO:K11489]
103607877  [KO:K11305] [EC:2.3.1.48]
103607913  [KO:K11459]
103608454  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103608619  [KO:K18491]
103608856  NEUROG1; neurogenin-1 [KO:K09081]
103608971  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
103609194  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
103609951  WNT7B; protein Wnt-7b [KO:K00572]
103609963  [KO:K10177]
103610513  HRAS; GTPase HRas isoform X1 [KO:K02833]
Reference
  Authors
Bhartiya D, Lenka N (ed).
  Title
Pluripotent Stem Cells
  Journal
InTech (2013)
DOI:10.5772/45917
Reference
  Authors
Hassani SN, Totonchi M, Gourabi H, Scholer HR, Baharvand H
  Title
Signaling roadmap modulating naive and primed pluripotency.
  Journal
Stem Cells Dev 23:193-208 (2014)
DOI:10.1089/scd.2013.0368
Reference
  Authors
Jaenisch R, Young R
  Title
Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming.
  Journal
Cell 132:567-82 (2008)
DOI:10.1016/j.cell.2008.01.015
Reference
  Authors
Zhang H, Wang ZZ
  Title
Mechanisms that mediate stem cell self-renewal and differentiation.
  Journal
J Cell Biochem 103:709-18 (2008)
DOI:10.1002/jcb.21460
Reference
  Authors
Itoh F, Watabe T, Miyazono K
  Title
Roles of TGF-beta family signals in the fate determination of pluripotent stem cells.
  Journal
Semin Cell Dev Biol 32C:98-106 (2014)
DOI:10.1016/j.semcdb.2014.05.017
Reference
  Authors
Saunders A, Faiola F, Wang J
  Title
Concise review: pursuing self-renewal and pluripotency with the stem cell factor Nanog.
  Journal
Stem Cells 31:1227-36 (2013)
DOI:10.1002/stem.1384
Reference
  Authors
Kuijk EW, Chuva de Sousa Lopes SM, Geijsen N, Macklon N, Roelen BA
  Title
The different shades of mammalian pluripotent stem cells.
  Journal
Hum Reprod Update 17:254-71 (2011)
DOI:10.1093/humupd/dmq035
Reference
  Authors
Okita K, Yamanaka S
  Title
Intracellular signaling pathways regulating pluripotency of embryonic stem cells.
  Journal
Curr Stem Cell Res Ther 1:103-11 (2006)
DOI:10.2174/157488806775269061
Reference
  Authors
Niwa H, Ogawa K, Shimosato D, Adachi K
  Title
A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells.
  Journal
Nature 460:118-22 (2009)
DOI:10.1038/nature08113
Reference
  Authors
Nakai-Futatsugi Y, Niwa H
  Title
Transcription factor network in embryonic stem cells: heterogeneity under the stringency.
  Journal
Biol Pharm Bull 36:166-70 (2013)
DOI:10.1248/bpb.b12-00958
Reference
  Authors
Medvedev SP, Shevchenko AI, Zakian SM
  Title
Molecular basis of Mammalian embryonic stem cell pluripotency and self-renewal.
  Journal
Acta Naturae 2:30-46 (2010)
Reference
  Authors
Scheper W, Copray S
  Title
The molecular mechanism of induced pluripotency: a two-stage switch.
  Journal
Stem Cell Rev 5:204-23 (2009)
DOI:10.1007/s12015-009-9077-x
Reference
  Authors
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
  Title
Core transcriptional regulatory circuitry in human embryonic stem cells.
  Journal
Cell 122:947-56 (2005)
DOI:10.1016/j.cell.2005.08.020
Reference
  Authors
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
  Title
The THO complex regulates pluripotency gene mRNA export and controls embryonic stem cell self-renewal and somatic cell reprogramming.
  Journal
Cell Stem Cell 13:676-90 (2013)
DOI:10.1016/j.stem.2013.10.008
Reference
  Authors
Hasegawa Y, Tang D, Takahashi N, Hayashizaki Y, Forrest AR, Suzuki H
  Title
CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes.
  Journal
Sci Rep 4:5228 (2014)
DOI:10.1038/srep05228
Reference
  Authors
Sui L, Bouwens L, Mfopou JK
  Title
Signaling pathways during maintenance and definitive endoderm differentiation of embryonic stem cells.
  Journal
Int J Dev Biol 57:1-12 (2013)
DOI:10.1387/ijdb.120115ls
Reference
  Authors
Do JT, Scholer HR
  Title
Regulatory circuits underlying pluripotency and reprogramming.
  Journal
Trends Pharmacol Sci 30:296-302 (2009)
DOI:10.1016/j.tips.2009.03.003
Reference
  Authors
Pan G, Thomson JA
  Title
Nanog and transcriptional networks in embryonic stem cell pluripotency.
  Journal
Cell Res 17:42-9 (2007)
DOI:10.1038/sj.cr.7310125
Reference
  Authors
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
  Title
The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.
  Journal
Nat Genet 38:431-40 (2006)
DOI:10.1038/ng1760
Reference
  Authors
Loh YH, Ng JH, Ng HH
  Title
Molecular framework underlying pluripotency.
  Journal
Cell Cycle 7:885-91 (2008)
DOI:10.4161/cc.7.7.5636
Reference
  Authors
Greenow K, Clarke AR
  Title
Controlling the stem cell compartment and regeneration in vivo: the role of pluripotency pathways.
  Journal
Physiol Rev 92:75-99 (2012)
DOI:10.1152/physrev.00040.2010
Related
pathway
gvr04010  MAPK signaling pathway
gvr04151  PI3K-Akt signaling pathway
gvr04310  Wnt signaling pathway
gvr04350  TGF-beta signaling pathway
gvr04630  JAK-STAT signaling pathway
KO pathway
ko04550   

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