KEGG   PATHWAY: aml04550
Entry
aml04550                    Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Ailuropoda melanoleuca (giant panda)
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
aml04550  Signaling pathways regulating pluripotency of stem cells
aml04550

Other DBs
GO: 2000036
Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100483416  LIF; leukemia inhibitory factor isoform X2 [KO:K05419]
100463863  LIFR; leukemia inhibitory factor receptor isoform X1 [KO:K05058]
100483131  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
100473460  JAK1; tyrosine-protein kinase JAK1 isoform X2 [KO:K11217] [EC:2.7.10.2]
100481360  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
100474005  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
100469938  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
100474186  KLF4; Krueppel-like factor 4 isoform X2 [KO:K17846]
100469604  SOX2; transcription factor SOX-2 [KO:K16796]
100464396  MYC; myc proto-oncogene protein [KO:K04377]
100468916  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
100478039  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100465700  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100463775  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100479294  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100479580  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100475291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100483828  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100467916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100468763  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100480414  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100465793  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100478252  TBX3; LOW QUALITY PROTEIN: T-box transcription factor TBX3 [KO:K10177]
100478621  NANOG; homeobox protein NANOG isoform X1 [KO:K10164]
100463717  INHBA; inhibin beta A chain [KO:K04667]
100484001  INHBB; LOW QUALITY PROTEIN: inhibin beta B chain [KO:K22687]
100477882  INHBC; inhibin beta C chain [KO:K22688]
100478138  INHBE; inhibin beta E chain [KO:K22689]
100481810  NODAL; nodal homolog isoform X1 [KO:K04666]
100482103  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
100476073  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
100472026  ACVR2A; activin receptor type-2A isoform X2 [KO:K04670] [EC:2.7.11.30]
100477787  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
100467069  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100479304  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100477715  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
100472999  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
100467049  BMPR1B; bone morphogenetic protein receptor type-1B isoform X2 [KO:K13578] [EC:2.7.11.30]
100476325  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
100483427  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
100479813  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
100467794  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
100475440  SMAD9; mothers against decapentaplegic homolog 9 isoform X2 [KO:K16791]
100465063  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
100470429  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
100481765  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
100476030  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
100478523  DUSP9; dual specificity protein phosphatase 9 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
100465223  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100465476  MAPK14; mitogen-activated protein kinase 14 isoform X3 [KO:K04441] [EC:2.7.11.24]
100480235  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100480483  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100475007  WNT1; proto-oncogene Wnt-1 [KO:K03209]
100480237  WNT2; protein Wnt-2 isoform X1 [KO:K00182]
100481665  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
100471555  WNT3; proto-oncogene Wnt-3 [KO:K00312]
100473835  WNT3A; protein Wnt-3a [KO:K00312]
100468584  WNT4; protein Wnt-4 [KO:K00408]
100484068  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
100473854  WNT5B; protein Wnt-5b isoform X3 [KO:K00444]
100467896  WNT6; protein Wnt-6 [KO:K00445]
100475153  WNT7A; protein Wnt-7a isoform X1 [KO:K00572]
100474982  WNT7B; protein Wnt-7b [KO:K00572]
100466672  WNT8B; protein Wnt-8b isoform X1 [KO:K00714]
100481684  WNT8A; LOW QUALITY PROTEIN: protein Wnt-8a [KO:K00714]
100472460  WNT9B; protein Wnt-9b [KO:K01064]
100475103  WNT9A; protein Wnt-9a isoform X1 [KO:K01064]
100467643  protein Wnt-10a isoform X1 [KO:K01357]
100475265  WNT10B; protein Wnt-10b isoform X1 [KO:K01357]
117795031  WNT10A; LOW QUALITY PROTEIN: protein Wnt-10a [KO:K01357]
100468561  WNT11; protein Wnt-11 [KO:K01384]
100464171  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
100469196  FZD1; frizzled-1 [KO:K02432]
109489608  FZD7; frizzled-7 [KO:K02432]
100469249  FZD2; frizzled-2 [KO:K02235]
100468831  FZD3; frizzled-3 isoform X1 [KO:K02329]
100470379  FZD4; frizzled-4 [KO:K02354]
100478649  FZD5; frizzled-5 [KO:K02375]
100467779  FZD8; frizzled-8 [KO:K02375]
100464621  FZD6; frizzled-6 isoform X1 [KO:K02376]
100479765  FZD10; frizzled-10 [KO:K02842]
100469765  FZD9; LOW QUALITY PROTEIN: frizzled-9 [KO:K02842]
100466067  DVL3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
100471972  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X2 [KO:K02353]
100480005  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
100479224  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
100473018  AXIN1; axin-1 isoform X1 [KO:K02157]
100477069  AXIN2; axin-2 isoform X1 [KO:K04385]
100472257  APC; adenomatous polyposis coli protein isoform X5 [KO:K02085]
100465768  APC2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
100477834  CTNNB1; catenin beta-1 [KO:K02105]
100479681  TCF3; transcription factor E2-alpha isoform X3 [KO:K09063]
100482227  ESRRB; steroid hormone receptor ERR2 isoform X2 [KO:K08553]
100476528  TCF7; transcription factor 7 isoform X2 [KO:K02620]
100480318  POU5F1; POU domain, class 5, transcription factor 1 [KO:K09367]
100475658  POU domain, class 5, transcription factor 1-like [KO:K09367]
100479986  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
100472630  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
100468267  FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
100481826  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
100477678  FGFR4; fibroblast growth factor receptor 4 [KO:K05095] [EC:2.7.10.1]
100473836  HRAS; GTPase HRas isoform X1 [KO:K02833]
100483919  KRAS; GTPase KRas isoform X1 [KO:K07827]
100464196  NRAS; GTPase NRas [KO:K07828]
100482255  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100473254  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
100471374  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
100463628  HESX1; homeobox expressed in ES cells 1 [KO:K09354]
100467160  ZIC3; zinc finger protein ZIC 3 isoform X1 [KO:K18487]
100477421  left-right determination factor 1-like isoform X1 [KO:K04668]
100474292  SKIL; ski-like protein isoform X1 [KO:K18499]
100466145  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.-]
100467992  KAT6A; LOW QUALITY PROTEIN: histone acetyltransferase KAT6A [KO:K11305] [EC:2.3.1.48]
100482250  SETDB1; histone-lysine N-methyltransferase SETDB1 isoform X1 [KO:K11421] [EC:2.1.1.366]
100470934  JARID2; protein Jumonji isoform X1 [KO:K11478]
100483588  REST; RE1-silencing transcription factor isoform X2 [KO:K09222]
100484381  RIF1; telomere-associated protein RIF1 isoform X4 [KO:K11138]
100472768  PCGF1; polycomb group RING finger protein 1 isoform X5 [KO:K11487]
100478058  PCGF2; polycomb group RING finger protein 2 [KO:K11460]
100481115  PCGF3; polycomb group RING finger protein 3 isoform X1 [KO:K11488]
100464971  BMI1; polycomb complex protein BMI-1 isoform X1 [KO:K11459]
100466321  PCGF5; polycomb group RING finger protein 5 isoform X1 [KO:K11489]
100478037  PCGF6; polycomb group RING finger protein 6 isoform X1 [KO:K11470]
100476632  PAX6; paired box protein Pax-6 isoform X1 [KO:K08031]
100465236  MEIS1; homeobox protein Meis1 isoform X2 [KO:K15613]
100469903  HOXA1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
100474534  HOXB1; homeobox protein Hox-B1 [KO:K09301]
105241915  HOXD1; homeobox protein Hox-D1 [KO:K09301]
100484632  LHX5; LIM/homeobox protein Lhx5 [KO:K18493]
100483015  OTX1; homeobox protein OTX1 [KO:K09326]
100478283  NEUROG1; neurogenin-1 [KO:K09081]
100470676  HAND1; heart- and neural crest derivatives-expressed protein 1 isoform X1 [KO:K09071]
100469197  DLX5; homeobox protein DLX-5 [KO:K18489]
100483248  MYF5; myogenic factor 5 [KO:K18484]
100468514  ONECUT1; hepatocyte nuclear factor 6 [KO:K08026]
100475643  ISL1; insulin gene enhancer protein ISL-1 [KO:K09370]
100481514  ZFHX3; zinc finger homeobox protein 3 isoform X1 [KO:K09378]
100482646  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
  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
aml04010  MAPK signaling pathway
aml04151  PI3K-Akt signaling pathway
aml04310  Wnt signaling pathway
aml04350  TGF-beta signaling pathway
aml04630  JAK-STAT signaling pathway
KO pathway
ko04550   
LinkDB

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