KEGG   PATHWAY: pvp04550
Entry
pvp04550                    Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Pteropus vampyrus (large flying 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
pvp04550  Signaling pathways regulating pluripotency of stem cells
pvp04550

Other DBs
GO: 2000036
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288762  ONECUT1; hepatocyte nuclear factor 6 isoform X1 [KO:K08026]
105288777  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
105288917  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
105289246  LHX5; LIM/homeobox protein Lhx5 [KO:K18493]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105289398  [KO:K10177]
105289544  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
105289617  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.-]
105289930  HAND1; heart- and neural crest derivatives-expressed protein 1 [KO:K09071]
105290060  HOXD1; homeobox protein Hox-D1 [KO:K09301]
105290083  ESRRB; steroid hormone receptor ERR2 isoform X1 [KO:K08553]
105290156  WNT16; protein Wnt-16 [KO:K01558]
105290270  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
105290328  CTNNB1; catenin beta-1 [KO:K02105]
105290434  WNT4; protein Wnt-4 [KO:K00408]
105290451  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
105290730  PCGF1; polycomb group RING finger protein 1 isoform X1 [KO:K11487]
105291051  WNT10A; protein Wnt-10a [KO:K01357]
105291052  WNT6; protein Wnt-6 isoform X2 [KO:K00445]
105291323  ACVR1; activin receptor type-1 isoform X2 [KO:K04675] [EC:2.7.11.30]
105291355  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
105291441  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
105291512  FZD3; frizzled-3 isoform X1 [KO:K02329]
105291542  RIF1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
105291557  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
105291730  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
105291733  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
105292297  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
105292561  MYC; myc proto-oncogene protein [KO:K04377]
105292611  LEFTY2; left-right determination factor 2 [KO:K04668]
105292640  SMAD2; mothers against decapentaplegic homolog 2 isoform X3 [KO:K04500]
105293091  PCGF5; polycomb group RING finger protein 5 isoform X1 [KO:K11489]
105293172  HOXA1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
105293293  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
105293353  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
105293516  FGFR4; fibroblast growth factor receptor 4 isoform X1 [KO:K05095] [EC:2.7.10.1]
105293567  TCF7; transcription factor 7 isoform X2 [KO:K02620]
105293590  NEUROG1; neurogenin-1 [KO:K09081]
105293596  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
105293607  WNT8A; protein Wnt-8a [KO:K00714]
105293704  PAX6; paired box protein Pax-6 isoform X1 [KO:K08031]
105293757  REST; RE1-silencing transcription factor [KO:K09222]
105293964  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
105293969  JARID2; protein Jumonji [KO:K11478]
105294059  KRAS; GTPase KRas isoform X2 [KO:K07827]
105294187  FZD4; frizzled-4 [KO:K02354]
105294190  DLX5; homeobox protein DLX-5 [KO:K18489]
105294540  PCGF6; polycomb group RING finger protein 6 [KO:K11470]
105294552  FZD1; frizzled-1 [KO:K02432]
105294927  BMI1; polycomb complex protein BMI-1 [KO:K11459]
105294978  WNT7A; protein Wnt-7a [KO:K00572]
105295332  KLF4; Krueppel-like factor 4 isoform X1 [KO:K17846]
105295433  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
105295478  APC; adenomatous polyposis coli protein isoform X3 [KO:K02085]
105295787  MEIS1; homeobox protein Meis1 isoform X1 [KO:K15613]
105295921  NANOG; homeobox protein NANOG [KO:K10164]
105296142  INHBB; inhibin beta B chain [KO:K22687]
105296550  NRAS; GTPase NRas isoform X1 [KO:K07828]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105296612  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
105296814  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
105297140  [KO:K02649]
105297256  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
105297527  WNT10B; protein Wnt-10b [KO:K01357]
105297529  WNT1; proto-oncogene Wnt-1 [KO:K03209]
105297627  WNT11; protein Wnt-11 [KO:K01384]
105297749  AXIN2; axin-2 [KO:K04385]
105298112  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
105298116  FZD7; frizzled-7 [KO:K02432]
105298360  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
105298400  FZD5; frizzled-5 [KO:K02375]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105299114  LIFR; leukemia inhibitory factor receptor [KO:K05058]
105299364  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105299568  FZD10; frizzled-10 [KO:K02842]
105299684  FZD9; frizzled-9 [KO:K02842]
105299856  HESX1; homeobox expressed in ES cells 1 [KO:K09354]
105299863  WNT5A; protein Wnt-5a isoform X5 [KO:K00444]
105299958  WNT3A; protein Wnt-3a [KO:K00312]
105300002  WNT9A; protein Wnt-9a [KO:K01064]
105300123  NODAL; nodal homolog [KO:K04666]
105300159  [KO:K04456] [EC:2.7.11.1]
105300315  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
105300873  FZD6; frizzled-6 isoform X1 [KO:K02376]
105300917  LIF; leukemia inhibitory factor [KO:K05419]
105301017  KAT6A; histone acetyltransferase KAT6A [KO:K11305] [EC:2.3.1.48]
105301035  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105301036  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105301291  ISL1; insulin gene enhancer protein ISL-1 [KO:K09370]
105301304  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105301844  PCGF3; polycomb group RING finger protein 3 isoform X1 [KO:K11488]
105301871  FGFR3; fibroblast growth factor receptor 3 [KO:K05094] [EC:2.7.10.1]
105301951  MYF5; myogenic factor 5 [KO:K18484]
105302044  WNT7B; protein Wnt-7b [KO:K00572]
105302256  TCF3; transcription factor E2-alpha [KO:K09063]
105302259  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
105302522  DUSP9; dual specificity protein phosphatase 9 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
105303192  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
105303215  INHBA; inhibin beta A chain [KO:K04667]
105303252  AXIN1; axin-1 isoform X1 [KO:K02157]
105303453  WNT3; proto-oncogene Wnt-3 [KO:K00312]
105303454  WNT9B; protein Wnt-9b [KO:K01064]
105303480  FZD2; frizzled-2 [KO:K02235]
105303599  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
105303858  SETDB1; histone-lysine N-methyltransferase SETDB1 [KO:K11421] [EC:2.1.1.366]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105304266  [KO:K18491]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105304667  WNT8B; protein Wnt-8b [KO:K00714]
105305501  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
105305561  [KO:K18491]
105305629  SKIL; ski-like protein [KO:K18499]
105305933  HRAS; GTPase HRas isoform X1 [KO:K02833]
105306294  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105307013  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
105307053  ZIC3; zinc finger protein ZIC 3 isoform X1 [KO:K18487]
105307126  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
105307149  FZD8; frizzled-8 [KO:K02375]
105307213  ZFHX3; zinc finger homeobox protein 3 [KO:K09378]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307255  HOXB1; homeobox protein Hox-B1 [KO:K09301]
105307373  INHBC; inhibin beta C chain [KO:K22688]
105307374  INHBE; inhibin beta E chain [KO:K22689]
105307378  SOX2; transcription factor SOX-2 [KO:K16796]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105308128  POU5F1; POU domain, class 5, transcription factor 1 [KO:K09367]
105308283  [KO:K04441] [EC:2.7.11.24]
105308371  PCGF2; polycomb group RING finger protein 2 isoform X1 [KO:K11460]
105308390  OTX1; homeobox protein OTX1 [KO:K09326]
105308466  WNT2; protein Wnt-2 [KO:K00182]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105309232  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
105309746  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
105310714  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
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
pvp04010  MAPK signaling pathway
pvp04151  PI3K-Akt signaling pathway
pvp04310  Wnt signaling pathway
pvp04350  TGF-beta signaling pathway
pvp04630  JAK-STAT signaling pathway
KO pathway
ko04550   

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