KEGG   PATHWAY: caty04550
Entry
caty04550                   Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Cercocebus atys (sooty mangabey)
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
caty04550  Signaling pathways regulating pluripotency of stem cells
caty04550

Other DBs
GO: 2000036
Organism
Cercocebus atys (sooty mangabey) [GN:caty]
Gene
105575713  LIF; leukemia inhibitory factor [KO:K05419]
105583447  LIFR; leukemia inhibitory factor receptor isoform X1 [KO:K05058]
105599628  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
105595926  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
105584100  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
105601679  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
105579724  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
105595567  KLF4; Krueppel-like factor 4 isoform X1 [KO:K17846]
105598954  SOX2; transcription factor SOX-2 [KO:K16796]
105588384  MYC; myc proto-oncogene protein [KO:K04377]
105577731  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
105601165  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105591800  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
105598233  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105598850  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105586383  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105580892  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105597716  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105571321  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105594576  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105599262  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105596769  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105597977  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105574942  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105592728  TBX3; T-box transcription factor TBX3 isoform X1 [KO:K10177]
105578504  homeobox protein NANOG [KO:K10164]
105571436  homeobox protein NANOG-like [KO:K10164]
105583091  NANOG; LOW QUALITY PROTEIN: homeobox protein NANOG [KO:K10164]
105596936  INHBA; inhibin beta A chain [KO:K04667]
105588110  INHBB; inhibin beta B chain [KO:K22687]
105587263  INHBC; inhibin beta C chain [KO:K22688]
105587259  INHBE; inhibin beta E chain [KO:K22689]
105597278  NODAL; nodal homolog isoform X1 [KO:K04666]
105580327  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
105576108  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
105575953  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
105573896  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
105592520  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
105600979  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
105586635  BMP4; bone morphogenetic protein 4 [KO:K04662]
105593672  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
105572359  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
105576010  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
105580204  BMPR2; LOW QUALITY PROTEIN: bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
105580754  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
105599809  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
105587863  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
105592487  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
105582232  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
105587552  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
105594998  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
105572598  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
105598736  DUSP9; dual specificity protein phosphatase 9 isoform X1 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
105592690  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
105592727  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105586882  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
105586884  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
105580466  WNT1; proto-oncogene Wnt-1 [KO:K03209]
105596373  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
105598480  WNT2; protein Wnt-2 [KO:K00182]
105585713  WNT3; proto-oncogene Wnt-3 [KO:K00312]
105597682  WNT3A; protein Wnt-3a [KO:K00312]
105595022  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
105585595  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
105582958  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
105587053  WNT6; protein Wnt-6 [KO:K00445]
105585815  WNT7A; protein Wnt-7a [KO:K00572]
105586922  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
105581836  WNT8B; protein Wnt-8b [KO:K00714]
105599827  WNT8A; protein Wnt-8a [KO:K00714]
105585688  WNT9B; protein Wnt-9b isoform X1 [KO:K01064]
105597681  WNT9A; protein Wnt-9a [KO:K01064]
105587052  WNT10A; protein Wnt-10a [KO:K01357]
105578717  WNT11; protein Wnt-11 [KO:K01384]
105598493  WNT16; protein Wnt-16 [KO:K01558]
105580045  FZD7; frizzled-7 [KO:K02432]
105573552  FZD1; frizzled-1 [KO:K02432]
105585328  FZD2; frizzled-2 [KO:K02235]
105579158  FZD3; frizzled-3 isoform X1 [KO:K02329]
105592956  FZD4; frizzled-4 [KO:K02354]
105580107  FZD5; frizzled-5 [KO:K02375]
105597016  FZD8; frizzled-8 [KO:K02375]
105586564  FZD6; frizzled-6 isoform X1 [KO:K02376]
105593364  FZD9; frizzled-9 [KO:K02842]
105591051  FZD10; frizzled-10 [KO:K02842]
105572428  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
105573979  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
105582670  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
105589738  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105574573  AXIN1; axin-1 isoform X1 [KO:K02157]
105573034  AXIN2; axin-2 isoform X1 [KO:K04385]
105590693  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
105591719  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
105573861  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
105591727  TCF3; transcription factor E2-alpha isoform X1 [KO:K09063]
105590883  ESRRB; steroid hormone receptor ERR2 isoform X1 [KO:K08553]
105599768  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
105600008  POU5F1; POU domain, class 5, transcription factor 1 [KO:K09367]
105595795  FGF2; fibroblast growth factor 2 [KO:K18497]
105590801  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
105577985  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
105585485  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
105581716  FGFR4; fibroblast growth factor receptor 4 isoform X1 [KO:K05095] [EC:2.7.10.1]
105577198  HRAS; GTPase HRas isoform X1 [KO:K02833]
105585038  KRAS; GTPase KRas isoform X1 [KO:K07827]
105596344  NRAS; GTPase NRas isoform X1 [KO:K07828]
105585803  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105573305  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
105594004  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
105585609  HESX1; homeobox expressed in ES cells 1 isoform X1 [KO:K09354]
105592693  ZIC3; zinc finger protein ZIC 3 [KO:K18487]
105576934  LEFTY2; left-right determination factor 2 isoform X1 [KO:K04668]
105576936  left-right determination factor 1-like [KO:K04668]
105586059  SKIL; ski-like protein isoform X1 [KO:K18499]
105572354  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.-]
105595763  KAT6A; histone acetyltransferase KAT6A isoform X1 [KO:K11305] [EC:2.3.1.48]
105590302  SETDB1; LOW QUALITY PROTEIN: histone-lysine N-methyltransferase SETDB1 [KO:K11421] [EC:2.1.1.366]
105572565  JARID2; protein Jumonji isoform X1 [KO:K11478]
105575092  REST; RE1-silencing transcription factor isoform X1 [KO:K09222]
105575974  RIF1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
105596866  PCGF1; polycomb group RING finger protein 1 isoform X1 [KO:K11487]
105579526  PCGF2; polycomb group RING finger protein 2 isoform X1 [KO:K11460]
105585508  PCGF3; LOW QUALITY PROTEIN: polycomb group RING finger protein 3 [KO:K11488]
105583795  BMI1; polycomb complex protein BMI-1 [KO:K11459]
105587135  PCGF5; polycomb group RING finger protein 5 isoform X1 [KO:K11489]
105581902  PCGF6; polycomb group RING finger protein 6 isoform X1 [KO:K11470]
105586761  PAX6; paired box protein Pax-6 isoform X1 [KO:K08031]
105576485  MEIS1; homeobox protein Meis1 isoform X1 [KO:K15613]
105579493  HOXB1; homeobox protein Hox-B1 [KO:K09301]
105579847  HOXD1; homeobox protein Hox-D1 [KO:K09301]
105595849  HOXA1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
105592722  LHX5; LIM/homeobox protein Lhx5 [KO:K18493]
105576454  OTX1; homeobox protein OTX1 [KO:K09326]
105599797  NEUROG1; neurogenin-1 [KO:K09081]
105589924  HAND1; heart- and neural crest derivatives-expressed protein 1 isoform X1 [KO:K09071]
105592208  DLX5; LOW QUALITY PROTEIN: homeobox protein DLX-5 [KO:K18489]
105581081  MYF5; myogenic factor 5 [KO:K18484]
105601133  ONECUT1; hepatocyte nuclear factor 6 [KO:K08026]
105571991  ISL1; insulin gene enhancer protein ISL-1 isoform X1 [KO:K09370]
105580095  ZFHX3; LOW QUALITY PROTEIN: zinc finger homeobox protein 3 [KO:K09378]
105571632  ESX1; homeobox protein ESX1 [KO:K18491]
105598366  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
caty04010  MAPK signaling pathway
caty04151  PI3K-Akt signaling pathway
caty04310  Wnt signaling pathway
caty04350  TGF-beta signaling pathway
caty04630  JAK-STAT signaling pathway
KO pathway
ko04550   
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