KEGG   PATHWAY: panu04550
Entry
panu04550                   Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Papio anubis (olive baboon)
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
panu04550  Signaling pathways regulating pluripotency of stem cells
panu04550

Other DBs
GO: 2000036
Organism
Papio anubis (olive baboon) [GN:panu]
Gene
101002040  LIF; leukemia inhibitory factor isoform X1 [KO:K05419]
101007792  LIFR; leukemia inhibitory factor receptor isoform X1 [KO:K05058]
100998383  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
101002872  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
101007171  JAK2; tyrosine-protein kinase JAK2 isoform X4 [KO:K04447] [EC:2.7.10.2]
101014985  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
100998929  STAT3; signal transducer and activator of transcription 3 isoform X9 [KO:K04692]
101018765  KLF4; Krueppel-like factor 4 isoform X2 [KO:K17846]
101022620  transcription factor SOX-2 [KO:K16796]
116273032  transcription factor SOX-2 [KO:K16796]
116273658  transcription factor SOX-2 [KO:K16796]
101000645  MYC; myc proto-oncogene protein [KO:K04377]
101002675  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101008394  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101004074  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101012041  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101006756  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101004976  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101008699  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101002278  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100510873  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X4 [KO:K02649]
101009981  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101002971  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100997634  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101000402  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100381179  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101020127  TBX3; T-box transcription factor TBX3 isoform X1 [KO:K10177]
103876808  homeobox protein NANOG [KO:K10164]
101016098  LOW QUALITY PROTEIN: homeobox protein NANOG [KO:K10164]
100997336  homeobox protein NANOG-like [KO:K10164]
103883110  homeobox protein NANOG [KO:K10164]
101025106  INHBA; inhibin beta A chain [KO:K04667]
101019223  INHBB; inhibin beta B chain [KO:K22687]
100997847  INHBC; inhibin beta C chain [KO:K22688]
100998203  INHBE; inhibin beta E chain [KO:K22689]
101016702  NODAL; nodal homolog [KO:K04666]
101020254  ACVR1B; activin receptor type-1B isoform X2 [KO:K13567] [EC:2.7.11.30]
101005651  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
101009691  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
101004271  ACVR2B; activin receptor type-2B isoform X3 [KO:K13596] [EC:2.7.11.30]
101004882  SMAD2; mothers against decapentaplegic homolog 2 isoform X2 [KO:K04500]
101013089  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100137596  BMP4; bone morphogenetic protein 4 precursor [KO:K04662]
101003417  BMPR1A; bone morphogenetic protein receptor type-1A isoform X1 [KO:K04673] [EC:2.7.11.30]
101008254  BMPR1B; bone morphogenetic protein receptor type-1B isoform X2 [KO:K13578] [EC:2.7.11.30]
101006461  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
101019906  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
101017482  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
101006755  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
101004769  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
101019266  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
101020825  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
101017423  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
101015982  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
101022995  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
101012857  DUSP9; dual specificity protein phosphatase 9 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
101001103  MAPK12; mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]
101002393  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101024189  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101024771  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101013629  WNT1; proto-oncogene Wnt-1 [KO:K03209]
101008897  WNT2B; protein Wnt-2b [KO:K00182]
100126674  WNT2; protein Wnt-2 precursor [KO:K00182]
101001727  WNT3; proto-oncogene Wnt-3 isoform X2 [KO:K00312]
101005424  WNT4; protein Wnt-4 [KO:K00408]
100997755  WNT5A; protein Wnt-5a isoform X2 [KO:K00444]
101019776  WNT5B; protein Wnt-5b [KO:K00444]
100997506  WNT6; protein Wnt-6 [KO:K00445]
101009898  WNT7B; protein Wnt-7b [KO:K00572]
101002180  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
101014279  WNT8A; protein Wnt-8a [KO:K00714]
101002037  WNT8B; protein Wnt-8b [KO:K00714]
100999626  WNT9A; protein Wnt-9a isoform X2 [KO:K01064]
101007522  WNT9B; protein Wnt-9b [KO:K01064]
100997855  WNT10A; protein Wnt-10a [KO:K01357]
101013252  WNT10B; protein Wnt-10b [KO:K01357]
101005798  WNT11; protein Wnt-11 [KO:K01384]
101022538  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
101015632  FZD7; frizzled-7 [KO:K02432]
100137461  FZD1; frizzled-1 [KO:K02432]
101011059  FZD2; frizzled-2 [KO:K02235]
101000744  FZD3; frizzled-3 isoform X1 [KO:K02329]
101013533  FZD4; frizzled-4 isoform X1 [KO:K02354]
101013139  FZD5; frizzled-5 [KO:K02375]
101012990  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
100999712  FZD6; frizzled-6 [KO:K02376]
101004836  FZD10; frizzled-10 [KO:K02842]
101010325  FZD9; frizzled-9 [KO:K02842]
101019485  DVL2; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
101007736  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X6 [KO:K02353]
101007009  DVL1; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
100998800  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101012942  AXIN2; axin-2 isoform X1 [KO:K04385]
101015820  APC; adenomatous polyposis coli protein isoform X7 [KO:K02085]
101014712  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
110741428  TCF3; LOW QUALITY PROTEIN: transcription factor E2-alpha [KO:K09063]
101000399  ESRRB; steroid hormone receptor ERR2 [KO:K08553]
101024089  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
101003706  POU5F1; LOW QUALITY PROTEIN: POU domain, class 5, transcription factor 1 [KO:K09367]
116272643  uncharacterized protein LOC116272643 isoform X1 [KO:K09367]
101003965  FGF2; fibroblast growth factor 2 isoform X1 [KO:K18497]
101002603  FGFR1; fibroblast growth factor receptor 1 isoform X6 [KO:K04362] [EC:2.7.10.1]
101002495  FGFR2; fibroblast growth factor receptor 2 isoform X12 [KO:K05093] [EC:2.7.10.1]
101014560  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
101025157  FGFR4; LOW QUALITY PROTEIN: fibroblast growth factor receptor 4 [KO:K05095] [EC:2.7.10.1]
101002992  HRAS; GTPase HRas isoform X2 [KO:K02833]
101017528  KRAS; GTPase KRas isoform X2 [KO:K07827]
101026253  NRAS; GTPase NRas isoform X2 [KO:K07828]
101009029  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101010276  IGF1; insulin-like growth factor I isoform X2 [KO:K05459]
100126735  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
101022039  HESX1; homeobox expressed in ES cells 1 [KO:K09354]
101015377  ZIC3; zinc finger protein ZIC 3 isoform X1 [KO:K18487]
101011357  left-right determination factor 2 [KO:K04668]
101011710  left-right determination factor 1 [KO:K04668]
101024514  SKIL; ski-like protein isoform X1 [KO:K18499]
101003490  SMARCAD1; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 isoform X2 [KO:K14439] [EC:5.6.2.-]
101017630  KAT6A; histone acetyltransferase KAT6A isoform X3 [KO:K11305] [EC:2.3.1.48]
101002056  SETDB1; histone-lysine N-methyltransferase SETDB1 isoform X1 [KO:K11421] [EC:2.1.1.366]
101012808  JARID2; protein Jumonji isoform X1 [KO:K11478]
101007427  REST; RE1-silencing transcription factor isoform X1 [KO:K09222]
101020129  RIF1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
101022151  PCGF1; polycomb group RING finger protein 1 [KO:K11487]
101022994  PCGF2; polycomb group RING finger protein 2 isoform X1 [KO:K11460]
101022599  PCGF3; polycomb group RING finger protein 3 [KO:K11488]
101025525  BMI1; polycomb complex protein BMI-1 isoform X1 [KO:K11459]
101002264  PCGF5; polycomb group RING finger protein 5 isoform X1 [KO:K11489]
101001915  PCGF6; polycomb group RING finger protein 6 isoform X1 [KO:K11470]
101024279  PAX6; paired box protein Pax-6 isoform X3 [KO:K08031]
101002172  MEIS1; homeobox protein Meis1 isoform X4 [KO:K15613]
101018620  HOXD1; homeobox protein Hox-D1 [KO:K09301]
101009727  HOXB1; homeobox protein Hox-B1 [KO:K09301]
100137568  HOXA1; homeobox protein Hox-A1 [KO:K09301]
101016716  LHX5; LIM/homeobox protein Lhx5 [KO:K18493]
101017304  OTX1; homeobox protein OTX1 [KO:K09326]
101000493  NEUROG1; neurogenin-1 [KO:K09081]
101002590  HAND1; heart- and neural crest derivatives-expressed protein 1 isoform X1 [KO:K09071]
101026286  DLX5; homeobox protein DLX-5 [KO:K18489]
101026712  MYF5; myogenic factor 5 [KO:K18484]
101009090  LOW QUALITY PROTEIN: hepatocyte nuclear factor 6 [KO:K08026]
116275831  hepatocyte nuclear factor 6 [KO:K08026]
101011645  ISL1; insulin gene enhancer protein ISL-1 isoform X2 [KO:K09370]
101017132  ZFHX3; zinc finger homeobox protein 3 isoform X2 [KO:K09378]
101009771  ESX1; homeobox protein ESX1 [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
panu04010  MAPK signaling pathway
panu04151  PI3K-Akt signaling pathway
panu04310  Wnt signaling pathway
panu04350  TGF-beta signaling pathway
panu04630  JAK-STAT signaling pathway
KO pathway
ko04550   
LinkDB

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