KEGG   PATHWAY: vlg04550
Entry
vlg04550                    Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Vulpes lagopus (Arctic fox)
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
vlg04550  Signaling pathways regulating pluripotency of stem cells
vlg04550

Other DBs
GO: 2000036
Organism
Vulpes lagopus (Arctic fox) [GN:vlg]
Gene
121475249  LIF; leukemia inhibitory factor isoform X1 [KO:K05419]
121487245  LIFR; leukemia inhibitory factor receptor isoform X1 [KO:K05058]
121496704  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
121499401  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
121483167  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
121494166  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
121473042  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
121496092  KLF4; Krueppel-like factor 4 [KO:K17846]
121477240  SOX2; transcription factor SOX-2 [KO:K16796]
121499098  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
121473934  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
121484067  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
121495470  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
121475510  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
121486545  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
121477352  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
121478805  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
121499678  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121481416  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
121496480  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
121494738  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
121488903  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121482033  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
121482375  LOW QUALITY PROTEIN: RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
121493415  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
121475605  TBX3; T-box transcription factor TBX3 isoform X1 [KO:K10177]
121481649  putative homeobox protein NANOG2 [KO:K10164]
121479751  NANOG; homeobox protein NANOG isoform X1 [KO:K10164]
121471299  INHBA; inhibin beta A chain [KO:K04667]
121482115  INHBB; inhibin beta B chain [KO:K22687]
121492009  INHBC; inhibin beta C chain [KO:K22688]
121492008  INHBE; inhibin beta E chain isoform X1 [KO:K22689]
121487806  NODAL; nodal homolog [KO:K04666]
121479981  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
121471362  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
121482017  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
121478737  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
121484675  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
121482745  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
121493806  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
121486306  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
121493624  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
121501474  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
121480503  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
121481168  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
121494878  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
121497378  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
121482063  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
121478079  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
121490391  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
121490883  LOW QUALITY PROTEIN: DNA-binding protein inhibitor ID-2-like [KO:K17693]
121496514  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
121500833  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
121482328  DUSP9; dual specificity protein phosphatase 9 isoform X1 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
121482054  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
121485950  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
121491672  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
121491673  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
121480178  WNT1; proto-oncogene Wnt-1 isoform X1 [KO:K03209]
121474438  WNT2; protein Wnt-2 isoform X1 [KO:K00182]
121490731  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
121474007  WNT3; proto-oncogene Wnt-3 [KO:K00312]
121474467  WNT3A; protein Wnt-3a [KO:K00312]
121498205  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
121479913  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
121495641  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
121480717  WNT6; protein Wnt-6 [KO:K00445]
121490476  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
121495152  WNT7A; protein Wnt-7a [KO:K00572]
121476849  WNT8B; protein Wnt-8b [KO:K00714]
121495235  WNT8A; protein Wnt-8a [KO:K00714]
121474006  WNT9B; protein Wnt-9b [KO:K01064]
121475053  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
121480841  WNT10A; protein Wnt-10a [KO:K01357]
121480042  WNT10B; protein Wnt-10b [KO:K01357]
121475935  WNT11; protein Wnt-11 [KO:K01384]
121474824  WNT16; protein Wnt-16 [KO:K01558]
121480659  FZD7; frizzled-7 isoform X1 [KO:K02432]
121474752  FZD1; frizzled-1 [KO:K02432]
121472594  FZD2; frizzled-2 [KO:K02235]
121498183  FZD3; frizzled-3 isoform X1 [KO:K02329]
121476036  FZD4; frizzled-4 isoform X1 [KO:K02354]
121480532  FZD5; frizzled-5 [KO:K02375]
121498057  FZD8; frizzled-8 [KO:K02375]
121498902  FZD6; frizzled-6 isoform X1 [KO:K02376]
121475662  FZD10; frizzled-10 [KO:K02842]
121486703  FZD9; frizzled-9 [KO:K02842]
121477470  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
121499761  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
121499953  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
121489623  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
121486746  AXIN1; axin-1 isoform X1 [KO:K02157]
121473774  AXIN2; axin-2 isoform X1 [KO:K04385]
121489860  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
121495587  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
121478755  CTNNB1; catenin beta-1 [KO:K02105]
121495597  TCF3; transcription factor E2-alpha isoform X1 [KO:K09063]
121493684  ESRRB; steroid hormone receptor ERR2 isoform X1 [KO:K08553]
121495797  TCF7; transcription factor 7 isoform X1 [KO:K02620]
121499434  POU5F1; POU domain, class 5, transcription factor 1 [KO:K09367]
121493095  FGF2; fibroblast growth factor 2 isoform X1 [KO:K18497]
121489119  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
121484320  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
121489705  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
121488199  FGFR4; fibroblast growth factor receptor 4 [KO:K05095] [EC:2.7.10.1]
121472124  HRAS; GTPase HRas isoform X1 [KO:K02833]
121479900  KRAS; GTPase KRas isoform X1 [KO:K07827]
121491321  NRAS; GTPase NRas [KO:K07828]
121494281  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
121481162  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
121490029  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
121495125  HESX1; homeobox expressed in ES cells 1 [KO:K09354]
121483401  ZIC3; zinc finger protein ZIC 3 isoform X1 [KO:K18487]
121501620  left-right determination factor 1-like isoform X1 [KO:K04668]
121477479  SKIL; ski-like protein isoform X1 [KO:K18499]
121493401  SMARCAD1; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 isoform X1 [KO:K14439] [EC:5.6.2.-]
121489134  KAT6A; histone acetyltransferase KAT6A isoform X1 [KO:K11305] [EC:2.3.1.48]
121490848  SETDB1; histone-lysine N-methyltransferase SETDB1 isoform X1 [KO:K11421] [EC:2.1.1.366]
121499540  JARID2; protein Jumonji isoform X1 [KO:K11478]
121473518  REST; RE1-silencing transcription factor [KO:K09222]
121481917  RIF1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
121491975  PCGF1; polycomb group RING finger protein 1 isoform X1 [KO:K11487]
121472583  PCGF2; polycomb group RING finger protein 2 isoform X1 [KO:K11460]
121489118  PCGF3; polycomb group RING finger protein 3 isoform X1 [KO:K11488]
121497537  BMI1; polycomb complex protein BMI-1 [KO:K11459]
121481115  PCGF5; polycomb group RING finger protein 5 isoform X1 [KO:K11489]
121484735  PCGF6; polycomb group RING finger protein 6 isoform X1 [KO:K11470]
121471426  PAX6; paired box protein Pax-6 isoform X1 [KO:K08031]
121491141  MEIS1; homeobox protein Meis1 isoform X1 [KO:K15613]
121473789  HOXB1; homeobox protein Hox-B1 [KO:K09301]
121474607  HOXA1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
121501285  HOXD1; homeobox protein Hox-D1 [KO:K09301]
121475263  LHX5; LIM/homeobox protein Lhx5 [KO:K18493]
121491911  OTX1; homeobox protein OTX1 [KO:K09326]
121494494  NEUROG1; neurogenin-1 [KO:K09081]
121486179  HAND1; heart- and neural crest derivatives-expressed protein 1 isoform X1 [KO:K09071]
121474892  DLX5; homeobox protein DLX-5 [KO:K18489]
121481153  MYF5; myogenic factor 5 [KO:K18484]
121484773  ONECUT1; hepatocyte nuclear factor 6 isoform X1 [KO:K08026]
121486268  ISL1; insulin gene enhancer protein ISL-1 isoform X1 [KO:K09370]
121500830  ZFHX3; zinc finger homeobox protein 3 isoform X1 [KO:K09378]
121482600  ESX1; homeobox protein ESX1 [KO:K18491]
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
vlg04010  MAPK signaling pathway
vlg04151  PI3K-Akt signaling pathway
vlg04310  Wnt signaling pathway
vlg04350  TGF-beta signaling pathway
vlg04630  JAK-STAT signaling pathway
KO pathway
ko04550   
LinkDB

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