KEGG   PATHWAY: bmus04550
Entry
bmus04550                   Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Balaenoptera musculus (blue whale)
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
bmus04550  Signaling pathways regulating pluripotency of stem cells
bmus04550

Other DBs
GO: 2000036
Organism
Balaenoptera musculus (blue whale) [GN:bmus]
Gene
118880317  LIF; leukemia inhibitory factor [KO:K05419]
118892303  LIFR; leukemia inhibitory factor receptor isoform X1 [KO:K05058]
118891872  IL6ST; LOW QUALITY PROTEIN: interleukin-6 receptor subunit beta [KO:K05060]
118895748  JAK1; LOW QUALITY PROTEIN: tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
118896614  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
118891748  JAK3; LOW QUALITY PROTEIN: tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
118887532  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
118893181  Krueppel-like factor 4 [KO:K17846]
118896885  KLF4; Krueppel-like factor 4 isoform X1 [KO:K17846]
118893889  SOX2; transcription factor SOX-2 [KO:K16796]
118883580  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
118886410  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
118891063  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
118892655  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
118880663  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
118906690  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
118892181  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118894592  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
118894671  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118891709  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118892996  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
118901944  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
118884787  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118900614  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118890216  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118880031  TBX3; T-box transcription factor TBX3 isoform X1 [KO:K10177]
118902119  NANOG; homeobox protein NANOG isoform X1 [KO:K10164]
118901048  INHBA; inhibin beta A chain [KO:K04667]
118898443  INHBB; inhibin beta B chain [KO:K22687]
118902308  INHBC; inhibin beta C chain [KO:K22688]
118902359  INHBE; inhibin beta E chain [KO:K22689]
118882698  NODAL; nodal homolog isoform X1 [KO:K04666]
118901903  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
118898108  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
118897886  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
118903018  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
118906922  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
118890561  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
118891260  BMP4; LOW QUALITY PROTEIN: bone morphogenetic protein 4 [KO:K04662]
118882590  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
118896016  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
118898176  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
118897810  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
118895584  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
118892310  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
118884323  SMAD9; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 9 [KO:K16791]
118906696  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
118881996  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
118906438  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
118885423  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
118904088  ID4; DNA-binding protein inhibitor ID-4 isoform X1 [KO:K17695]
118888702  DUSP9; dual specificity protein phosphatase 9 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
118904356  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
118904357  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
118901762  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
118901763  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
118902702  WNT1; proto-oncogene Wnt-1 [KO:K03209]
118900444  WNT2; protein Wnt-2 [KO:K00182]
118887326  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
118892954  WNT3A; protein Wnt-3a [KO:K00312]
118886840  WNT3; proto-oncogene Wnt-3 [KO:K00312]
118895516  WNT4; protein Wnt-4 isoform X1 [KO:K00408]
118904326  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
118902166  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
118898154  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
118902847  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
118903109  WNT7A; protein Wnt-7a [KO:K00572]
118892532  WNT8A; protein Wnt-8a [KO:K00714]
118882652  WNT8B; protein Wnt-8b [KO:K00714]
118886662  WNT9B; protein Wnt-9b [KO:K01064]
118893397  WNT9A; protein Wnt-9a [KO:K01064]
118897747  WNT10A; protein Wnt-10a isoform X1 [KO:K01357]
118902265  WNT10B; protein Wnt-10b [KO:K01357]
118900158  WNT11; protein Wnt-11 isoform X1 [KO:K01384]
118900824  WNT16; protein Wnt-16 [KO:K01558]
118898248  FZD7; frizzled-7 [KO:K02432]
118900455  FZD1; frizzled-1 [KO:K02432]
118886169  FZD2; frizzled-2 [KO:K02235]
118897387  FZD3; frizzled-3 isoform X1 [KO:K02329]
118899439  FZD4; frizzled-4 isoform X1 [KO:K02354]
118891047  FZD8; frizzled-8 [KO:K02375]
118894594  FZD5; frizzled-5 [KO:K02375]
118883840  FZD6; frizzled-6 isoform X1 [KO:K02376]
118880344  FZD10; frizzled-10 [KO:K02842]
118881326  FZD9; frizzled-9 [KO:K02842]
118886461  DVL2; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
118893584  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
118894624  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
118894954  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
118881169  AXIN1; axin-1 isoform X1 [KO:K02157]
118886265  AXIN2; axin-2 isoform X1 [KO:K04385]
118891954  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
118892175  APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
118903019  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
118891851  TCF3; transcription factor E2-alpha isoform X1 [KO:K09063]
118891326  ESRRB; steroid hormone receptor ERR2 isoform X1 [KO:K08553]
118892102  TCF7; transcription factor 7 isoform X1 [KO:K02620]
118895851  LOW QUALITY PROTEIN: POU domain, class 5, transcription factor 1-like [KO:K09367]
118903668  POU5F1; POU domain, class 5, transcription factor 1 [KO:K09367]
118895460  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
118887767  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
118882534  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
118895440  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
118893430  FGFR4; fibroblast growth factor receptor 4 isoform X1 [KO:K05095] [EC:2.7.10.1]
118892044  GTPase HRas-like [KO:K02833]
118899209  HRAS; GTPase HRas isoform X1 [KO:K02833]
118901791  KRAS; GTPase KRas isoform X1 [KO:K07827]
118893681  NRAS; GTPase NRas [KO:K07828]
118904127  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
118901824  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
118890679  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
118903737  HESX1; homeobox expressed in ES cells 1 isoform X1 [KO:K09354]
118888639  ZIC3; zinc finger protein ZIC 3 isoform X1 [KO:K18487]
118892451  LOW QUALITY PROTEIN: left-right determination factor 2-like [KO:K04668]
118905941  left-right determination factor 2-like isoform X1 [KO:K04668]
118894303  SKIL; ski-like protein isoform X1 [KO:K18499]
118902196  LOW QUALITY PROTEIN: ski-like protein [KO:K18499]
118895926  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.-]
118887764  KAT6A; histone acetyltransferase KAT6A [KO:K11305] [EC:2.3.1.48]
118897508  SETDB1; histone-lysine N-methyltransferase SETDB1 isoform X1 [KO:K11421] [EC:2.1.1.366]
118903413  JARID2; LOW QUALITY PROTEIN: protein Jumonji [KO:K11478]
118895580  LOW QUALITY PROTEIN: RE1-silencing transcription factor-like [KO:K09222]
118895754  RE1-silencing transcription factor-like [KO:K09222]
118897779  RIF1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
118905871  PCGF1; polycomb group RING finger protein 1 [KO:K11487]
118887275  PCGF2; polycomb group RING finger protein 2 isoform X1 [KO:K11460]
118895604  PCGF3; polycomb group RING finger protein 3 isoform X1 [KO:K11488]
118890446  BMI1; polycomb complex protein BMI-1 [KO:K11459]
118890956  LOW QUALITY PROTEIN: polycomb group RING finger protein 5-like [KO:K11489]
118882496  PCGF5; LOW QUALITY PROTEIN: polycomb group RING finger protein 5 [KO:K11489]
118882597  PCGF6; polycomb group RING finger protein 6 isoform X1 [KO:K11470]
118899155  PAX6; paired box protein Pax-6 isoform X1 [KO:K08031]
118906384  MEIS1; homeobox protein Meis1 isoform X1 [KO:K15613]
118897727  HOXD1; homeobox protein Hox-D1 isoform X1 [KO:K09301]
118887007  HOXB1; homeobox protein Hox-B1 [KO:K09301]
118900881  HOXA1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
118880091  LHX5; LIM/homeobox protein Lhx5 [KO:K18493]
118905635  OTX1; LOW QUALITY PROTEIN: homeobox protein OTX1 [KO:K09326]
118891802  NEUROG1; neurogenin-1 [KO:K09081]
118892878  HAND1; heart- and neural crest derivatives-expressed protein 1 isoform X1 [KO:K09071]
118900425  DLX5; homeobox protein DLX-5 [KO:K18489]
118901909  MYF5; myogenic factor 5 [KO:K18484]
118890411  ONECUT1; hepatocyte nuclear factor 6 [KO:K08026]
118893232  ISL1; insulin gene enhancer protein ISL-1 [KO:K09370]
118885235  ZFHX3; zinc finger homeobox protein 3 [KO:K09378]
118888223  ESX1; homeobox protein ESX1 [KO:K18491]
118888350  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
bmus04010  MAPK signaling pathway
bmus04151  PI3K-Akt signaling pathway
bmus04310  Wnt signaling pathway
bmus04350  TGF-beta signaling pathway
bmus04630  JAK-STAT signaling pathway
KO pathway
ko04550   
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