KEGG   PATHWAY: ray04550
Entry
ray04550                    Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Rousettus aegyptiacus (Egyptian rousette)
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
ray04550  Signaling pathways regulating pluripotency of stem cells
ray04550

Other DBs
GO: 2000036
Organism
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
Gene
107505402  LIF; leukemia inhibitory factor isoform X1 [KO:K05419]
107515246  LIFR; LOW QUALITY PROTEIN: leukemia inhibitory factor receptor [KO:K05058]
107509633  IL6ST; interleukin-6 receptor subunit beta [KO:K05060]
107518627  interleukin-6 receptor subunit beta-like [KO:K05060]
107517940  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
107507294  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
107521798  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
107513823  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
107502639  KLF4; Krueppel-like factor 4 isoform X1 [KO:K17846]
107507031  SOX2; transcription factor SOX-2 [KO:K16796]
107506202  MYC; myc proto-oncogene protein [KO:K04377]
107503781  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
107508942  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
107510634  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
107515836  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
107497830  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107520152  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107517828  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
107513958  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107521668  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
107517899  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
107498704  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
107513978  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107521783  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107498395  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107517128  TBX3; T-box transcription factor TBX3 isoform X1 [KO:K10177]
107501668  NANOG; homeobox protein NANOG isoform X1 [KO:K10164]
107502403  INHBA; inhibin beta A chain [KO:K04667]
107501434  INHBB; inhibin beta B chain [KO:K22687]
107501520  INHBC; inhibin beta C chain [KO:K22688]
107501519  INHBE; inhibin beta E chain [KO:K22689]
107498203  NODAL; nodal homolog [KO:K04666]
107509821  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
107513428  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
107513936  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
107499637  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
107512663  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
107508935  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
107509544  BMP4; bone morphogenetic protein 4 [KO:K04662]
107509897  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
107510637  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
107513429  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
107519367  BMPR2; LOW QUALITY PROTEIN: bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
107520351  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
107506827  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
107503946  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
107512852  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
107512890  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
107498274  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
107501042  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
107512834  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
107504709  DUSP9; dual specificity protein phosphatase 9 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
107497883  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
107497895  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
107500264  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
107500274  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
107514294  WNT1; proto-oncogene Wnt-1 [KO:K03209]
107505364  WNT2; protein Wnt-2 isoform X1 [KO:K00182]
107499803  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
107509667  WNT3A; protein Wnt-3a [KO:K00312]
107508173  WNT3; proto-oncogene Wnt-3 [KO:K00312]
107513057  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
107503411  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
107500582  WNT5B; protein Wnt-5b [KO:K00444]
107516780  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
107505517  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
107502411  WNT7A; protein Wnt-7a [KO:K00572]
107518710  WNT8A; LOW QUALITY PROTEIN: protein Wnt-8a [KO:K00714]
107499773  WNT8B; protein Wnt-8b [KO:K00714]
107509675  WNT9A; protein Wnt-9a [KO:K01064]
107508172  WNT9B; protein Wnt-9b [KO:K01064]
107514289  WNT10B; protein Wnt-10b [KO:K01357]
107516694  WNT10A; protein Wnt-10a [KO:K01357]
107519202  WNT11; LOW QUALITY PROTEIN: protein Wnt-11 [KO:K01384]
107500238  WNT16; protein Wnt-16 [KO:K01558]
107519374  FZD7; frizzled-7 [KO:K02432]
107500880  FZD1; frizzled-1 [KO:K02432]
107508108  FZD2; frizzled-2 [KO:K02235]
107510778  FZD3; frizzled-3 isoform X1 [KO:K02329]
107518567  FZD4; frizzled-4 [KO:K02354]
107505121  FZD8; frizzled-8 [KO:K02375]
107505167  FZD5; frizzled-5 [KO:K02375]
107512212  FZD6; frizzled-6 [KO:K02376]
107511767  FZD9; frizzled-9 [KO:K02842]
107511534  FZD10; frizzled-10 [KO:K02842]
107507013  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
107509513  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
107510646  DVL1; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
107517741  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
107506131  AXIN1; axin-1 isoform X1 [KO:K02157]
107510301  AXIN2; axin-2 isoform X1 [KO:K04385]
107500934  APC2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
107512008  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
107519993  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
107500893  TCF3; transcription factor E2-alpha [KO:K09063]
107516680  ESRRB; steroid hormone receptor ERR2 isoform X1 [KO:K08553]
107506797  TCF7; transcription factor 7 isoform X1 [KO:K02620]
107506214  POU5F1; POU domain, class 5, transcription factor 1 [KO:K09367]
107518501  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
107515961  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
107512997  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
107518024  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
107517559  FGFR4; fibroblast growth factor receptor 4 isoform X1 [KO:K05095] [EC:2.7.10.1]
107507127  HRAS; GTPase HRas isoform X1 [KO:K02833]
107497434  KRAS; GTPase KRas isoform X1 [KO:K07827]
107499847  NRAS; LOW QUALITY PROTEIN: GTPase NRas [KO:K07828]
107519729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
107501166  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
107509347  insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
107503392  HESX1; homeobox expressed in ES cells 1 [KO:K09354]
107506465  ZIC3; zinc finger protein ZIC 3 [KO:K18487]
107517083  LEFTY2; left-right determination factor 2 isoform X1 [KO:K04668]
107517098  left-right determination factor 2-like isoform X1 [KO:K04668]
107501409  SKIL; ski-like protein isoform X1 [KO:K18499]
107510630  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.-]
107501323  KAT6A; histone acetyltransferase KAT6A [KO:K11305] [EC:2.3.1.48]
107499036  SETDB1; histone-lysine N-methyltransferase SETDB1 isoform X1 [KO:K11421] [EC:2.1.1.366]
107502648  JARID2; LOW QUALITY PROTEIN: protein Jumonji [KO:K11478]
107517714  REST; RE1-silencing transcription factor [KO:K09222]
107513919  RIF1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
107502919  PCGF1; polycomb group RING finger protein 1 isoform X1 [KO:K11487]
107520717  PCGF2; polycomb group RING finger protein 2 isoform X1 [KO:K11460]
107518000  PCGF3; polycomb group RING finger protein 3 isoform X1 [KO:K11488]
107499931  BMI1; polycomb complex protein BMI-1 [KO:K11459]
107513997  PCGF5; LOW QUALITY PROTEIN: polycomb group RING finger protein 5 [KO:K11489]
107515562  PCGF6; polycomb group RING finger protein 6 [KO:K11470]
107512006  PAX6; paired box protein Pax-6 isoform X1 [KO:K08031]
107506939  MEIS1; homeobox protein Meis1 isoform X1 [KO:K15613]
107520631  HOXB1; homeobox protein Hox-B1 [KO:K09301]
107505667  HOXA1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
107504911  HOXD1; homeobox protein Hox-D1 [KO:K09301]
107517116  LHX5; LIM/homeobox protein Lhx5 [KO:K18493]
107519874  OTX1; homeobox protein OTX1 [KO:K09326]
107506794  NEUROG1; neurogenin-1 [KO:K09081]
107521938  HAND1; heart- and neural crest derivatives-expressed protein 1 [KO:K09071]
107504484  DLX5; homeobox protein DLX-5 [KO:K18489]
107503691  MYF5; myogenic factor 5 [KO:K18484]
107515161  ONECUT1; hepatocyte nuclear factor 6 [KO:K08026]
107509612  ISL1; insulin gene enhancer protein ISL-1 [KO:K09370]
107511917  ZFHX3; LOW QUALITY PROTEIN: zinc finger homeobox protein 3 [KO:K09378]
107508049  rhox homeobox family member 2-like [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
ray04010  MAPK signaling pathway
ray04151  PI3K-Akt signaling pathway
ray04310  Wnt signaling pathway
ray04350  TGF-beta signaling pathway
ray04630  JAK-STAT signaling pathway
KO pathway
ko04550   
LinkDB

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