KEGG   PATHWAY: plop04550
Entry
plop04550                   Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Perognathus longimembris pacificus (Pacific pocket mouse)
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
plop04550  Signaling pathways regulating pluripotency of stem cells
plop04550

Other DBs
GO: 2000036
Organism
Perognathus longimembris pacificus (Pacific pocket mouse) [GN:plop]
Gene
125347994  Lif; leukemia inhibitory factor [KO:K05419]
125367822  Lifr; leukemia inhibitory factor receptor isoform X1 [KO:K05058]
125367391  Il6st; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
125355256  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
125339535  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
125348908  Jak3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
125366353  Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
125346224  Klf4; Krueppel-like factor 4 isoform X1 [KO:K17846]
125351327  Sox2; transcription factor SOX-2 [KO:K16796]
125360808  Myc; myc proto-oncogene protein [KO:K04377]
125365698  Grb2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
125340362  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
125348606  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
125340801  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125349325  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125354550  Pik3cd; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
125342393  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
125351954  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
125367817  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125355095  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
125348916  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
125338979  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125363440  LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
125363452  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125359645  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125349085  Tbx3; T-box transcription factor TBX3 isoform X1 [KO:K10177]
125345748  Inhba; inhibin beta A chain [KO:K04667]
125368397  Inhbb; inhibin beta B chain [KO:K22687]
125362380  Inhbc; inhibin beta C chain [KO:K22688]
125354296  Inhbe; inhibin beta E chain [KO:K22689]
125343337  Nodal; nodal homolog [KO:K04666]
125364542  Acvr1b; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
125350654  Acvr1c; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
125350695  Acvr2a; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
125342448  Acvr2b; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
125364233  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
125341157  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
125363324  Bmp4; bone morphogenetic protein 4 [KO:K04662]
125346539  Bmpr1a; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
125341654  Bmpr1b; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
125350651  Acvr1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
125350388  Bmpr2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
125341415  Smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
125341882  Smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
125343989  mothers against decapentaplegic homolog 5-like isoform X1 [KO:K16790]
125348347  Smad9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
125364252  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
125353352  Id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
125356753  Id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
125354712  Id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
125352982  Id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
125343466  Dusp9; dual specificity protein phosphatase 9 isoform X1 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
125356681  Mapk11; LOW QUALITY PROTEIN: mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
125357039  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
125352181  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
125352654  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
125354832  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
125355394  Wnt2b; protein Wnt-2b [KO:K00182]
125345855  Wnt2; protein Wnt-2 [KO:K00182]
125359884  Wnt3a; protein Wnt-3a [KO:K00312]
125366521  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
125354690  Wnt4; protein Wnt-4 [KO:K00408]
125342888  Wnt5b; LOW QUALITY PROTEIN: protein Wnt-5b [KO:K00444]
125358571  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
125345203  LOW QUALITY PROTEIN: protein Wnt-5b-like [KO:K00444]
125349902  Wnt6; protein Wnt-6 [KO:K00445]
125353585  Wnt7b; LOW QUALITY PROTEIN: protein Wnt-7b [KO:K00572]
125358150  Wnt7a; protein Wnt-7a [KO:K00572]
125367604  Wnt8a; protein Wnt-8a [KO:K00714]
125346158  Wnt8b; protein Wnt-8b [KO:K00714]
125359441  Wnt9a; protein Wnt-9a [KO:K01064]
125366286  Wnt9b; protein Wnt-9b [KO:K01064]
125354833  Wnt10b; protein Wnt-10b [KO:K01357]
125349901  Wnt10a; protein Wnt-10a [KO:K01357]
125345094  protein Wnt-11-like [KO:K01384]
125361901  Wnt11; LOW QUALITY PROTEIN: protein Wnt-11 [KO:K01384]
125345859  Wnt16; protein Wnt-16 [KO:K01558]
125346990  Fzd1; frizzled-1 [KO:K02432]
125350393  Fzd7; frizzled-7 [KO:K02432]
125366002  Fzd2; frizzled-2 [KO:K02235]
125339272  Fzd3; frizzled-3 [KO:K02329]
125361251  Fzd4; frizzled-4 [KO:K02354]
125367210  Fzd8; frizzled-8 [KO:K02375]
125350351  Fzd5; frizzled-5 [KO:K02375]
125360684  Fzd6; frizzled-6 [KO:K02376]
125347985  Fzd10; frizzled-10 [KO:K02842]
125350799  Fzd9; frizzled-9 [KO:K02842]
125354458  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
125365205  Dvl2; LOW QUALITY PROTEIN: segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
125352052  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
125351736  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
125341178  Axin1; axin-1 isoform X1 [KO:K02157]
125365778  Axin2; axin-2 [KO:K04385]
125340098  Apc; adenomatous polyposis coli protein isoform X1 [KO:K02085]
125348497  Apc2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
125342497  Ctnnb1; catenin beta-1 [KO:K02105]
125348488  Tcf3; transcription factor E2-alpha isoform X1 [KO:K09063]
125363307  Esrrb; steroid hormone receptor ERR2 isoform X1 [KO:K08553]
125342174  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
125352796  Pou5f1; POU domain, class 5, transcription factor 1 [KO:K09367]
125341650  Fgf2; fibroblast growth factor 2 [KO:K18497]
125339698  Fgfr1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
125345313  fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
125345984  Fgfr2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
125364429  Fgfr3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
125341968  Fgfr4; fibroblast growth factor receptor 4 isoform X1 [KO:K05095] [EC:2.7.10.1]
125362333  Hras; GTPase HRas isoform X1 [KO:K02833]
125342925  Kras; GTPase KRas isoform X1 [KO:K07827]
125355453  Nras; GTPase NRas [KO:K07828]
125358819  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125359379  Igf1; insulin-like growth factor I isoform X1 [KO:K05459]
125368530  Igf1r; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
125358564  Hesx1; homeobox expressed in ES cells 1 [KO:K09354]
125343847  Zic3; zinc finger protein ZIC 3 isoform X1 [KO:K18487]
125359622  LOW QUALITY PROTEIN: left-right determination factor 2-like [KO:K04668]
125359704  left-right determination factor 2-like isoform X1 [KO:K04668]
125351987  Skil; ski-like protein [KO:K18499]
125341426  Smarcad1; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 [KO:K14439] [EC:5.6.2.-]
125339316  Kat6a; histone acetyltransferase KAT6A isoform X1 [KO:K11305] [EC:2.3.1.48]
125360015  Setdb1; histone-lysine N-methyltransferase SETDB1 isoform X1 [KO:K11421] [EC:2.1.1.366]
125353005  Jarid2; protein Jumonji isoform X1 [KO:K11478]
125364421  Rest; RE1-silencing transcription factor isoform X1 [KO:K09222]
125350681  Rif1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
125356377  Pcgf1; polycomb group RING finger protein 1 isoform X1 [KO:K11487]
125366504  Pcgf2; polycomb group RING finger protein 2 isoform X1 [KO:K11460]
125364476  Pcgf3; polycomb group RING finger protein 3 isoform X1 [KO:K11488]
125366841  Bmi1; polycomb complex protein BMI-1 [KO:K11459]
125346286  Pcgf5; polycomb group RING finger protein 5 isoform X1 [KO:K11489]
125346096  Pcgf6; polycomb group RING finger protein 6 isoform X1 [KO:K11470]
125361390  Pax6; paired box protein Pax-6 isoform X1 [KO:K08031]
125356269  Meis1; homeobox protein Meis1 isoform X1 [KO:K15613]
125346796  Hoxa1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
125349972  Hoxd1; homeobox protein Hox-D1 [KO:K09301]
125365876  Hoxb1; homeobox protein Hox-B1 [KO:K09301]
125347980  Lhx5; LIM/homeobox protein Lhx5 [KO:K18493]
125356852  Otx1; homeobox protein OTX1 [KO:K09326]
125342205  Neurog1; neurogenin-1 [KO:K09081]
125342152  Hand1; heart- and neural crest derivatives-expressed protein 1 isoform X1 [KO:K09071]
125345841  Dlx5; homeobox protein DLX-5 isoform X1 [KO:K18489]
125347538  Myf5; myogenic factor 5 [KO:K18484]
125340894  Onecut1; hepatocyte nuclear factor 6 [KO:K08026]
125367646  Isl1; insulin gene enhancer protein ISL-1 isoform X1 [KO:K09370]
125358227  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
plop04010  MAPK signaling pathway
plop04151  PI3K-Akt signaling pathway
plop04310  Wnt signaling pathway
plop04350  TGF-beta signaling pathway
plop04630  JAK-STAT signaling pathway
KO pathway
ko04550   
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