KEGG   PATHWAY: opi04550
Entry
opi04550                    Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Ochotona princeps (American pika)
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
opi04550  Signaling pathways regulating pluripotency of stem cells
opi04550

Other DBs
GO: 2000036
Organism
Ochotona princeps (American pika) [GN:opi]
Gene
101520848  LIF; leukemia inhibitory factor [KO:K05419]
101533811  LIFR; leukemia inhibitory factor receptor [KO:K05058]
101523596  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
101535293  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101518245  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
101527090  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
101528287  STAT3; signal transducer and activator of transcription 3 isoform X2 [KO:K04692]
101535347  KLF4; Krueppel-like factor 4 [KO:K17846]
101529551  SOX2; transcription factor SOX-2 [KO:K16796]
101522285  MYC; myc proto-oncogene protein [KO:K04377]
101531037  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
101533612  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105942099  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
101529486  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101530701  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101525427  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101519449  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101533851  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
101533024  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101532354  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101517982  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101528030  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101533296  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101519021  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101525801  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101527592  TBX3; T-box transcription factor TBX3 isoform X1 [KO:K10177]
101534419  NANOG; homeobox protein NANOG [KO:K10164]
101522112  INHBA; inhibin beta A chain [KO:K04667]
101536762  INHBB; inhibin beta B chain [KO:K22687]
101523426  INHBC; inhibin beta C chain [KO:K22688]
101523675  INHBE; inhibin beta E chain [KO:K22689]
101516650  NODAL; nodal homolog [KO:K04666]
101527295  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
101528913  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
101536630  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
101535616  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
101529841  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
101532983  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
101531889  BMP4; LOW QUALITY PROTEIN: bone morphogenetic protein 4 [KO:K04662]
101534297  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
101522569  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
101528675  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
101519164  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
101521562  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
101531816  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
101527268  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
101525575  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
101517899  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
101518290  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
101528492  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
101536782  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
101519826  DUSP9; dual specificity protein phosphatase 9 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
101525120  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101525684  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101524339  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101524571  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
101526533  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101519545  WNT2; protein Wnt-2 [KO:K00182]
101535993  WNT2B; protein Wnt-2b [KO:K00182]
101531097  WNT3A; protein Wnt-3a [KO:K00312]
101519718  WNT3; proto-oncogene Wnt-3 [KO:K00312]
101532229  WNT4; protein Wnt-4 [KO:K00408]
101533147  WNT5B; protein Wnt-5b [KO:K00444]
101526139  WNT5A; protein Wnt-5a [KO:K00444]
101518428  WNT6; protein Wnt-6 [KO:K00445]
101525411  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
101527317  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
101535038  WNT8A; protein Wnt-8a [KO:K00714]
101530831  WNT8B; protein Wnt-8b [KO:K00714]
101535462  WNT9A; protein Wnt-9a [KO:K01064]
101519468  WNT9B; protein Wnt-9b [KO:K01064]
101526780  WNT10B; protein Wnt-10b [KO:K01357]
101518185  WNT10A; protein Wnt-10a [KO:K01357]
101530628  WNT11; protein Wnt-11 isoform X1 [KO:K01384]
101521646  WNT16; protein Wnt-16 [KO:K01558]
101528861  FZD1; frizzled-1 [KO:K02432]
101519819  FZD7; frizzled-7 [KO:K02432]
101520542  FZD2; frizzled-2 [KO:K02235]
101528374  FZD3; frizzled-3 [KO:K02329]
101518239  FZD4; frizzled-4 [KO:K02354]
101532093  FZD5; frizzled-5 [KO:K02375]
101517741  FZD8; frizzled-8 [KO:K02375]
101524151  FZD6; frizzled-6 [KO:K02376]
101519524  FZD9; frizzled-9 [KO:K02842]
101520287  FZD10; frizzled-10 [KO:K02842]
101522688  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
101528918  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
101516456  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
101533693  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101533051  AXIN1; axin-1 isoform X1 [KO:K02157]
101522655  AXIN2; axin-2 isoform X1 [KO:K04385]
101516222  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
101526321  APC; adenomatous polyposis coli protein [KO:K02085]
101528934  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
101533529  TCF3; transcription factor E2-alpha isoform X1 [KO:K09063]
101524868  ESRRB; steroid hormone receptor ERR2 isoform X3 [KO:K08553]
101526730  TCF7; transcription factor 7 isoform X2 [KO:K02620]
101527772  POU5F1; POU domain, class 5, transcription factor 1 [KO:K09367]
101520285  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
101534918  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
101531872  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
101521291  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
101523935  FGFR4; fibroblast growth factor receptor 4 isoform X1 [KO:K05095] [EC:2.7.10.1]
101531636  HRAS; GTPase HRas [KO:K02833]
101534080  KRAS; GTPase KRas isoform X1 [KO:K07827]
101524465  NRAS; GTPase NRas [KO:K07828]
101534290  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101526004  IGF1; insulin-like growth factor I isoform X2 [KO:K05459]
101535483  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
101527203  HESX1; homeobox expressed in ES cells 1 [KO:K09354]
101527565  ZIC3; zinc finger protein ZIC 3 [KO:K18487]
101529338  LEFTY1; left-right determination factor 1 isoform X1 [KO:K04668]
101519336  LOW QUALITY PROTEIN: ski-like protein [KO:K18499]
101533908  SKIL; ski-like protein [KO:K18499]
101524727  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.-]
101517425  KAT6A; histone acetyltransferase KAT6A [KO:K11305] [EC:2.3.1.48]
101525521  SETDB1; histone-lysine N-methyltransferase SETDB1 isoform X1 [KO:K11421] [EC:2.1.1.366]
101519210  JARID2; protein Jumonji [KO:K11478]
101533757  REST; RE1-silencing transcription factor [KO:K09222]
101522265  RIF1; telomere-associated protein RIF1 [KO:K11138]
101536601  PCGF1; polycomb group RING finger protein 1 [KO:K11487]
101522734  PCGF2; polycomb group RING finger protein 2 [KO:K11460]
101523099  PCGF3; polycomb group RING finger protein 3 [KO:K11488]
101518514  BMI1; polycomb complex protein BMI-1 [KO:K11459]
101520985  PCGF5; polycomb group RING finger protein 5 isoform X1 [KO:K11489]
101535673  PCGF6; polycomb group RING finger protein 6 isoform X1 [KO:K11470]
101524707  PAX6; paired box protein Pax-6 isoform X3 [KO:K08031]
101517133  MEIS1; homeobox protein Meis1 isoform X1 [KO:K15613]
101517469  HOXA1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
101516601  HOXB1; homeobox protein Hox-B1 [KO:K09301]
101532340  HOXD1; homeobox protein Hox-D1 [KO:K09301]
101528506  LHX5; LIM/homeobox protein Lhx5 [KO:K18493]
101521687  OTX1; homeobox protein OTX1 isoform X1 [KO:K09326]
101531098  NEUROG1; neurogenin-1 [KO:K09081]
101529292  HAND1; heart- and neural crest derivatives-expressed protein 1 isoform X1 [KO:K09071]
101516250  DLX5; homeobox protein DLX-5 isoform X1 [KO:K18489]
101529852  MYF5; myogenic factor 5 [KO:K18484]
101516394  ONECUT1; hepatocyte nuclear factor 6 [KO:K08026]
101519851  ISL1; insulin gene enhancer protein ISL-1 isoform X1 [KO:K09370]
101533632  ZFHX3; LOW QUALITY PROTEIN: zinc finger homeobox protein 3 [KO:K09378]
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
opi04010  MAPK signaling pathway
opi04151  PI3K-Akt signaling pathway
opi04310  Wnt signaling pathway
opi04350  TGF-beta signaling pathway
opi04630  JAK-STAT signaling pathway
KO pathway
ko04550   
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