KEGG   PATHWAY: lve04550
Entry
lve04550                    Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Lipotes vexillifer (Yangtze River dolphin)
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
lve04550  Signaling pathways regulating pluripotency of stem cells
lve04550

Other DBs
GO: 2000036
Organism
Lipotes vexillifer (Yangtze River dolphin) [GN:lve]
Gene
103087024  LIF; leukemia inhibitory factor [KO:K05419]
103079546  LIFR; leukemia inhibitory factor receptor [KO:K05058]
103075698  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
103072682  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
103076804  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
103081519  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
103086495  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
103070688  KLF4; Krueppel-like factor 4-like isoform X1 [KO:K17846]
103076684  transcription factor SOX-2-like [KO:K16796]
103089962  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
103079766  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
103082805  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
103090769  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103070260  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
103075543  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103089257  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103088756  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103085303  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103070370  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103078725  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103083960  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103084975  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103076365  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103068921  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103084351  LOW QUALITY PROTEIN: T-box transcription factor TBX3-like [KO:K10177]
103083184  NANOG; homeobox protein NANOG [KO:K10164]
103091071  INHBA; LOW QUALITY PROTEIN: inhibin beta A chain [KO:K04667]
103078346  INHBB; inhibin beta B chain [KO:K22687]
103070514  INHBC; inhibin beta C chain [KO:K22688]
103070245  INHBE; inhibin beta E chain [KO:K22689]
103082126  NODAL; nodal homolog [KO:K04666]
103076167  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
103084357  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
103079492  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
103087212  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
103069124  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
103085090  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
103072786  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
103068998  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
103077119  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
103085459  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
103089843  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
103081175  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
103082423  SMAD5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
103070398  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
103084261  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
103081985  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
103089355  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
103081513  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
103090432  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
103089447  DUSP9; LOW QUALITY PROTEIN: dual specificity protein phosphatase 9 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
103083209  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103077530  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103078049  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103078710  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103078640  WNT1; proto-oncogene Wnt-1 [KO:K03209]
103089709  WNT2B; protein Wnt-2b [KO:K00182]
103089326  WNT2; protein Wnt-2 [KO:K00182]
103087738  WNT3A; protein Wnt-3a [KO:K00312]
103081536  WNT3; proto-oncogene Wnt-3 [KO:K00312]
103087836  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
103070287  WNT5A; protein Wnt-5a-like isoform X1 [KO:K00444]
103086235  WNT5B; protein Wnt-5b [KO:K00444]
103079243  WNT6; protein Wnt-6 [KO:K00445]
103083305  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
103068582  WNT7A; protein Wnt-7a [KO:K00572]
103086715  WNT8B; protein Wnt-8b [KO:K00714]
103091305  WNT8A; protein Wnt-8a [KO:K00714]
103087468  WNT9A; protein Wnt-9a [KO:K01064]
103081263  WNT9B; protein Wnt-9b [KO:K01064]
103078970  WNT10A; protein Wnt-10a [KO:K01357]
103078356  WNT10B; protein Wnt-10b [KO:K01357]
103091035  WNT11; protein Wnt-11 [KO:K01384]
103085163  WNT16; protein Wnt-16 [KO:K01558]
103091081  FZD7; frizzled-7 [KO:K02432]
103086341  FZD1; frizzled-1 [KO:K02432]
103076632  frizzled-2-like [KO:K02235]
103079251  FZD3; frizzled-3 [KO:K02329]
103086596  FZD4; frizzled-4 [KO:K02354]
103088051  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
103087849  FZD5; frizzled-5 [KO:K02375]
103074920  FZD6; frizzled-6 isoform X1 [KO:K02376]
103081501  FZD10; LOW QUALITY PROTEIN: frizzled class receptor 10 [KO:K02842]
103080648  FZD9; frizzled-9 [KO:K02842]
103082466  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
103078766  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
103086975  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
103074757  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103085333  AXIN1; axin-1 [KO:K02157]
103072027  AXIN2; axin-2 [KO:K04385]
103084983  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
103083467  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
103078301  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
103083785  TCF3; transcription factor E2-alpha isoform X1 [KO:K09063]
103087569  ESRRB; steroid hormone receptor ERR2 isoform X1 [KO:K08553]
103074150  TCF7; transcription factor 7 [KO:K02620]
103077875  POU5F1; POU domain, class 5, transcription factor 1 [KO:K09367]
103090898  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
103069902  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
103090812  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
103086424  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
103078406  FGFR4; fibroblast growth factor receptor 4 isoform X1 [KO:K05095] [EC:2.7.10.1]
103076043  HRAS; GTPase HRas isoform X1 [KO:K02833]
103077579  KRAS; GTPase KRas [KO:K07827]
103068734  NRAS; GTPase NRas [KO:K07828]
103087933  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103078928  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
103081291  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
103085128  HESX1; homeobox expressed in ES cells 1 [KO:K09354]
103069169  ZIC3; LOW QUALITY PROTEIN: zinc finger protein ZIC 3 [KO:K18487]
103072481  LEFTY2; left-right determination factor 2 isoform X1 [KO:K04668]
103073398  left-right determination factor 2-like isoform X1 [KO:K04668]
103088319  SKIL; ski-like protein isoform X1 [KO:K18499]
103078625  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.-]
103070015  KAT6A; histone acetyltransferase KAT6A [KO:K11305] [EC:2.3.1.48]
103076461  SETDB1; histone-lysine N-methyltransferase SETDB1 isoform X1 [KO:K11421] [EC:2.1.1.366]
103068915  JARID2; LOW QUALITY PROTEIN: protein Jumonji [KO:K11478]
103078260  REST; RE1-silencing transcription factor-like isoform X1 [KO:K09222]
103090669  RE1-silencing transcription factor-like isoform X1 [KO:K09222]
103082877  RIF1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
103084890  PCGF1; polycomb group RING finger protein 1 [KO:K11487]
103091319  PCGF2; polycomb group RING finger protein 2 [KO:K11460]
103090626  PCGF3; polycomb group RING finger protein 3 [KO:K11488]
103072022  BMI1; polycomb complex protein BMI-1 [KO:K11459]
103085085  PCGF5; polycomb group RING finger protein 5-like isoform X1 [KO:K11489]
103083110  PCGF6; polycomb group RING finger protein 6 isoform X1 [KO:K11470]
103070651  PAX6; paired box protein Pax-6 isoform X1 [KO:K08031]
103070577  MEIS1; homeobox protein Meis2 isoform X1 [KO:K15613]
103069992  HOXD1; homeobox protein Hox-D1 [KO:K09301]
103077583  HOXA1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
103083079  HOXB1; homeobox protein Hox-B1 [KO:K09301]
103083733  LHX5; LIM/homeobox protein Lhx5 [KO:K18493]
103077296  OTX1; homeobox protein OTX1 isoform X1 [KO:K09326]
103080509  NEUROG1; neurogenin-1 [KO:K09081]
103072384  HAND1; heart- and neural crest derivatives-expressed protein 1 [KO:K09071]
103072728  DLX5; homeobox protein DLX-5 [KO:K18489]
103079311  MYF5; myogenic factor 5 [KO:K18484]
103090061  ONECUT1; hepatocyte nuclear factor 6 [KO:K08026]
103069810  ISL1; insulin gene enhancer protein ISL-1 [KO:K09370]
103069757  ZFHX3; zinc finger homeobox protein 3 [KO:K09378]
103090446  ESX1; homeobox protein ESX1 [KO:K18491]
103080138  homeobox protein ESX1-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
lve04010  MAPK signaling pathway
lve04151  PI3K-Akt signaling pathway
lve04310  Wnt signaling pathway
lve04350  TGF-beta signaling pathway
lve04630  JAK-STAT signaling pathway
KO pathway
ko04550   
LinkDB

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