KEGG   PATHWAY: ecb04550
Entry
ecb04550                    Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Equus caballus (horse)
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
ecb04550  Signaling pathways regulating pluripotency of stem cells
ecb04550

Other DBs
GO: 2000036
Organism
Equus caballus (horse) [GN:ecb]
Gene
100629131  LIF; leukemia inhibitory factor isoform X1 [KO:K05419]
100066903  LIFR; leukemia inhibitory factor receptor [KO:K05058]
100051700  IL6ST; interleukin-6 receptor subunit beta precursor [KO:K05060]
100054008  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
100051487  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
100147451  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
100034011  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
100054047  KLF4; Krueppel-like factor 4 isoform X2 [KO:K17846]
100146979  SOX2; transcription factor SOX-2 [KO:K16796]
100068097  MYC; myc proto-oncogene protein [KO:K04377]
100051866  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100065996  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
100063190  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100057701  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
100066173  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100051623  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100058141  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100051753  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100052122  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100050227  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
100146348  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100064671  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100054961  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100061130  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100056019  TBX3; T-box transcription factor TBX3 isoform X1 [KO:K10177]
100061006  NANOG; homeobox protein NANOG [KO:K10164]
100034076  INHBA; inhibin beta A chain precursor [KO:K04667]
100067535  INHBB; inhibin beta B chain [KO:K22687]
100053175  INHBC; inhibin beta C chain [KO:K22688]
100050257  INHBE; inhibin beta E chain [KO:K22689]
100072735  NODAL; nodal homolog [KO:K04666]
100062619  ACVR1B; activin receptor type-1B isoform X2 [KO:K13567] [EC:2.7.11.30]
100059573  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
100049823  ACVR2A; activin receptor type-2A precursor [KO:K04670] [EC:2.7.11.30]
100053588  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
100033843  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100033845  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100034048  BMP4; bone morphogenetic protein 4 precursor [KO:K04662]
100064367  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
100053554  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
100050899  ACVR1; activin receptor type-1 isoform X2 [KO:K04675] [EC:2.7.11.30]
100067195  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
100033850  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
100033851  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
100062493  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
100033846  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
100068419  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
100057240  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
100071592  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
100066589  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
100057759  DUSP9; dual specificity protein phosphatase 9 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
100056278  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
100056239  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100063532  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
106782258  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100058859  WNT1; proto-oncogene Wnt-1 [KO:K03209]
100063931  WNT2B; protein Wnt-2b [KO:K00182]
100056092  WNT2; protein Wnt-2 precursor [KO:K00182]
100049880  WNT3; proto-oncogene Wnt-3 [KO:K00312]
100061145  WNT3A; protein Wnt-3a [KO:K00312]
100071678  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
100056017  WNT5B; protein Wnt-5b [KO:K00444]
100059157  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
100058824  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
100053027  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
100055450  WNT7A; protein Wnt-7a [KO:K00572]
111768287  protein Wnt-7a [KO:K00572]
100070360  WNT8B; protein Wnt-8b [KO:K00714]
100072609  WNT8A; protein Wnt-8a isoform X3 [KO:K00714]
100061110  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
100063730  WNT9B; protein Wnt-9b [KO:K01064]
100051649  WNT10B; protein Wnt-10b [KO:K01357]
111773843  WNT10A; protein Wnt-10a [KO:K01357]
100064184  WNT11; protein Wnt-11 [KO:K01384]
100071393  WNT16; protein Wnt-16 [KO:K01558]
102147960  FZD7; frizzled-7 [KO:K02432]
106783041  FZD1; frizzled-1 [KO:K02432]
100050809  FZD2; frizzled-2 [KO:K02235]
100054732  FZD3; frizzled-3 [KO:K02329]
100050465  FZD4; frizzled-4 [KO:K02354]
100146215  FZD5; frizzled-5 [KO:K02375]
111771171  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
100056351  FZD6; frizzled-6 [KO:K02376]
100062909  FZD10; frizzled-10 [KO:K02842]
100061635  FZD9; frizzled-9 [KO:K02842]
100061612  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
100147200  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
100147654  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
100061033  GSK3B; glycogen synthase kinase-3 beta isoform X6 [KO:K03083] [EC:2.7.11.26]
100065116  AXIN1; axin-1 isoform X1 [KO:K02157]
100630049  AXIN2; axin-2 [KO:K04385]
100064431  APC; adenomatous polyposis coli protein [KO:K02085]
100147102  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
100055241  CTNNB1; catenin beta-1 [KO:K02105]
100147220  TCF3; transcription factor E2-alpha isoform X1 [KO:K09063]
100058699  ESRRB; steroid hormone receptor ERR2 isoform X1 [KO:K08553]
100072786  TCF7; transcription factor 7 isoform X1 [KO:K02620]
100050785  POU5F1; POU domain, class 5, transcription factor 1 isoform X1 [KO:K09367]
100033955  FGF2; fibroblast growth factor 2 [KO:K18497]
100057614  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
100033956  FGFR2; fibroblast growth factor receptor 2 precursor [KO:K05093] [EC:2.7.10.1]
100034114  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
100068679  FGFR4; fibroblast growth factor receptor 4 isoform X2 [KO:K05095] [EC:2.7.10.1]
100055481  HRAS; GTPase HRas isoform X1 [KO:K02833]
100064473  KRAS; GTPase KRas isoform X1 [KO:K07827]
100051785  LOW QUALITY PROTEIN: GTPase KRas-like [KO:K07827]
100059469  NRAS; GTPase NRas [KO:K07828]
100051110  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100034198  IGF1; insulin-like growth factor I precursor [KO:K05459]
100055698  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
100050967  HESX1; homeobox expressed in ES cells 1 [KO:K09354]
100054537  ZIC3; zinc finger protein ZIC 3 isoform X1 [KO:K18487]
100147245  left-right determination factor 1 [KO:K04668]
100054366  left-right determination factor 1-like isoform X1 [KO:K04668]
100057606  SKIL; ski-like protein [KO:K18499]
100053412  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.-]
100050371  KAT6A; histone acetyltransferase KAT6A isoform X1 [KO:K11305] [EC:2.3.1.48]
100059254  SETDB1; histone-lysine N-methyltransferase SETDB1 isoform X1 [KO:K11421] [EC:2.1.1.366]
100051819  JARID2; protein Jumonji isoform X2 [KO:K11478]
100058152  REST; RE1-silencing transcription factor [KO:K09222]
100057721  RIF1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
100053783  PCGF1; polycomb group RING finger protein 1 isoform X2 [KO:K11487]
100055282  PCGF2; polycomb group RING finger protein 2 isoform X1 [KO:K11460]
100051730  PCGF3; polycomb group RING finger protein 3 [KO:K11488]
102148742  polycomb complex protein BMI-1 [KO:K11459]
100062658  polycomb group RING finger protein 5 isoform X1 [KO:K11489]
100062041  PCGF5; polycomb group RING finger protein 5 isoform X1 [KO:K11489]
100069783  PCGF6; polycomb group RING finger protein 6 isoform X2 [KO:K11470]
100146390  PAX6; paired box protein Pax-6 isoform X1 [KO:K08031]
100051257  MEIS1; homeobox protein Meis1 isoform X2 [KO:K15613]
100068884  HOXA1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
100069386  HOXB1; homeobox protein Hox-B1 [KO:K09301]
100066405  HOXD1; homeobox protein Hox-D1 [KO:K09301]
100056306  LHX5; LIM/homeobox protein Lhx5 [KO:K18493]
100051685  OTX1; homeobox protein OTX1 isoform X2 [KO:K09326]
100072700  NEUROG1; neurogenin-1 [KO:K09081]
100071390  HAND1; heart- and neural crest derivatives-expressed protein 1 [KO:K09071]
100052263  DLX5; homeobox protein DLX-5 [KO:K18489]
100060703  MYF5; myogenic factor 5 [KO:K18484]
100069457  ONECUT1; hepatocyte nuclear factor 6 [KO:K08026]
100052482  ISL1; insulin gene enhancer protein ISL-1 [KO:K09370]
100054244  ZFHX3; zinc finger homeobox protein 3 [KO:K09378]
102147825  ESX1; homeobox protein ESX1 [KO:K18491]
106781385  rhox homeobox family member 2 [KO:K18491]
Reference
  Authors
Bhartiya D, Lenka N (ed).
  Title
Pluripotent Stem Cells
  Journal
InTech (2013)
DOI:10.5772/45917
Reference
PMID:24147644
  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
PMID:18295576
  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
PMID:17647265
  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
PMID:24910449
  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
PMID:23653415
  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
PMID:20705693
  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
PMID:18220859
  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
PMID:19571885
  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
PMID:23370346
  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
PMID:22649650
  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
PMID:19551525
  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
PMID:16153702
  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
PMID:24315442
  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
PMID:24957798
  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
PMID:23585347
  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
PMID:19427042
  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
PMID:17211451
  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
PMID:16518401
  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
PMID:18414030
  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
PMID:22298652
  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
ecb04010  MAPK signaling pathway
ecb04151  PI3K-Akt signaling pathway
ecb04310  Wnt signaling pathway
ecb04350  TGF-beta signaling pathway
ecb04630  JAK-STAT signaling pathway
KO pathway
ko04550   
LinkDB

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