KEGG   PATHWAY: morg04550
Entry
morg04550                   Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Microtus oregoni (creeping vole)
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
morg04550  Signaling pathways regulating pluripotency of stem cells
morg04550

Other DBs
GO: 2000036
Organism
Microtus oregoni (creeping vole) [GN:morg]
Gene
121459648  leukemia inhibitory factor [KO:K05419]
121436491  leukemia inhibitory factor [KO:K05419]
121432874  Lifr; leukemia inhibitory factor receptor [KO:K05058]
121455663  Il6st; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
121448662  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
121454099  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
121462728  Jak3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
121442318  Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
121451924  Klf4; Krueppel-like factor 4 [KO:K17846]
121452971  Sox2; transcription factor SOX-2 [KO:K16796]
121461531  Myc; myc proto-oncogene protein [KO:K04377]
121463365  growth factor receptor-bound protein 2-like [KO:K04364]
121436142  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
121466018  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
121459389  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
121458143  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
121464725  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
121464321  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121453059  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
121448116  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121441780  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform-like [KO:K00922] [EC:2.7.1.153]
121455952  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
121462841  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
121448002  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
121434429  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
121449224  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121435875  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121446288  Tbx3; T-box transcription factor TBX3 isoform X1 [KO:K10177]
121443480  Nanog; homeobox protein NANOG [KO:K10164]
121432625  Inhba; inhibin beta A chain [KO:K04667]
121446115  Inhbb; inhibin beta B chain [KO:K22687]
121462871  Inhbc; inhibin beta C chain [KO:K22688]
121455747  Inhbe; inhibin beta E chain [KO:K22689]
121451131  Nodal; nodal homolog [KO:K04666]
121444245  Acvr1b; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
121433253  Acvr1c; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
121433139  Acvr2a; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
121464277  Acvr2b; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
121438761  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
121466030  Smad3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
121434984  Bmp4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
121455006  Bmpr1a; bone morphogenetic protein receptor type-1A isoform X1 [KO:K04673] [EC:2.7.11.30]
121446008  Bmpr1b; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
121433255  Acvr1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
121459053  bone morphogenetic protein receptor type-2-like isoform X1 [KO:K04671] [EC:2.7.11.30]
121445144  bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
121455828  Smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
121453312  mothers against decapentaplegic homolog 5 [KO:K16790]
121444920  mothers against decapentaplegic homolog 5 [KO:K16790]
121452848  Smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
121438756  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
121460289  Id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
121432379  Id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
121448422  Id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
121443271  Id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
121437255  dual specificity protein phosphatase 9-like [KO:K18498] [EC:3.1.3.16 3.1.3.48]
121440312  dual specificity protein phosphatase 9-like [KO:K18498] [EC:3.1.3.16 3.1.3.48]
121461212  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
121461365  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
121435212  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
121435574  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
121441513  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
121463415  Wnt2; protein Wnt-2 [KO:K00182]
121437971  Wnt2b; protein Wnt-2b [KO:K00182]
121457172  Wnt3a; protein Wnt-3a [KO:K00312]
121436221  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
121448785  Wnt4; protein Wnt-4 [KO:K00408]
121455289  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
121435324  Wnt5b; protein Wnt-5b [KO:K00444]
121447393  Wnt6; protein Wnt-6 isoform X1 [KO:K00445]
121461270  Wnt7b; protein Wnt-7b isoform X1 [KO:K00572]
121465932  Wnt7a; protein Wnt-7a isoform X1 [KO:K00572]
121454090  Wnt8b; protein Wnt-8b [KO:K00714]
121453656  protein Wnt-8a [KO:K00714]
121442954  protein Wnt-8a-like [KO:K00714]
121456099  Wnt9a; protein Wnt-9a [KO:K01064]
121436027  Wnt9b; protein Wnt-9b [KO:K01064]
121447471  Wnt10a; protein Wnt-10a [KO:K01357]
121441477  Wnt10b; protein Wnt-10b [KO:K01357]
121459039  protein Wnt-11 isoform X1 [KO:K01384]
121450881  protein Wnt-11 isoform X1 [KO:K01384]
121463445  Wnt16; protein Wnt-16 [KO:K01558]
121458637  frizzled-7 [KO:K02432]
121458999  frizzled-1 [KO:K02432]
121445141  frizzled-7 [KO:K02432]
121434768  frizzled-1 [KO:K02432]
121436322  Fzd2; frizzled-2 [KO:K02235]
121458839  Fzd3; frizzled-3 isoform X1 [KO:K02329]
121446844  Fzd4; frizzled-4 [KO:K02354]
121447041  Fzd8; frizzled-8 [KO:K02375]
121433430  Fzd5; frizzled-5 [KO:K02375]
121437706  Fzd6; frizzled-6 [KO:K02376]
121446230  Fzd9; frizzled-9 [KO:K02842]
121446467  Fzd10; frizzled-10 [KO:K02842]
121456540  Dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
121464917  Dvl3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
121448306  segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
121443553  segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
121461919  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
121463835  Axin1; axin-1 isoform X1 [KO:K02157]
121436256  Axin2; axin-2 isoform X1 [KO:K04385]
121459412  Apc2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085]
121453526  adenomatous polyposis coli protein isoform X1 [KO:K02085]
121443013  adenomatous polyposis coli protein-like isoform X1 [KO:K02085]
121464283  Ctnnb1; catenin beta-1 [KO:K02105]
121459425  Tcf3; transcription factor E2-alpha isoform X1 [KO:K09063]
121452317  Esrrb; steroid hormone receptor ERR2 isoform X1 [KO:K08553]
121456269  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
121435622  Pou5f1; POU domain, class 5, transcription factor 1 [KO:K09367]
121452838  Fgf2; fibroblast growth factor 2 [KO:K18497]
121462200  Fgfr1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
121457506  Fgfr2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
121459483  fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
121436445  fibroblast growth factor receptor 3-like isoform X1 [KO:K05094] [EC:2.7.10.1]
121444101  LOW QUALITY PROTEIN: fibroblast growth factor receptor 3-like [KO:K05094] [EC:2.7.10.1]
121445397  LOW QUALITY PROTEIN: fibroblast growth factor receptor 3-like [KO:K05094] [EC:2.7.10.1]
121445442  LOW QUALITY PROTEIN: fibroblast growth factor receptor 3-like [KO:K05094] [EC:2.7.10.1]
121445462  LOW QUALITY PROTEIN: fibroblast growth factor receptor 3-like [KO:K05094] [EC:2.7.10.1]
121445490  LOW QUALITY PROTEIN: fibroblast growth factor receptor 3-like [KO:K05094] [EC:2.7.10.1]
121445507  LOW QUALITY PROTEIN: fibroblast growth factor receptor 3-like [KO:K05094] [EC:2.7.10.1]
121445523  LOW QUALITY PROTEIN: fibroblast growth factor receptor 3-like [KO:K05094] [EC:2.7.10.1]
121453266  Fgfr4; fibroblast growth factor receptor 4 [KO:K05095] [EC:2.7.10.1]
121458090  Hras; GTPase HRas [KO:K02833]
121466497  Kras; GTPase KRas isoform X1 [KO:K07827]
121437938  Nras; GTPase NRas [KO:K07828]
121443425  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
121461353  Igf1; insulin-like growth factor I isoform X1 [KO:K05459]
121453621  Igf1r; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
121455355  Hesx1; homeobox expressed in ES cells 1 [KO:K09354]
121437357  zinc finger protein ZIC 3 [KO:K18487]
121437537  zinc finger protein ZIC 3-like isoform X1 [KO:K18487]
121435784  left-right determination factor 1 [KO:K04668]
121435929  left-right determination factor 2 [KO:K04668]
121452749  Skil; ski-like protein isoform X1 [KO:K18499]
121439940  Smarcad1; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 [KO:K14439] [EC:5.6.2.-]
121462380  Kat6a; histone acetyltransferase KAT6A [KO:K11305] [EC:2.3.1.48]
121450501  histone-lysine N-methyltransferase SETDB1 [KO:K11421] [EC:2.1.1.366]
121437839  histone-lysine N-methyltransferase SETDB1 [KO:K11421] [EC:2.1.1.366]
121434145  Jarid2; protein Jumonji isoform X1 [KO:K11478]
121460801  Rest; RE1-silencing transcription factor [KO:K09222]
121433179  Rif1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
121438585  Pcgf1; polycomb group RING finger protein 1 [KO:K11487]
121456872  Pcgf2; polycomb group RING finger protein 2 [KO:K11460]
121442482  polycomb group RING finger protein 2 [KO:K11460]
121433650  Pcgf3; polycomb group RING finger protein 3 isoform X1 [KO:K11488]
121432618  Bmi1; polycomb complex protein BMI-1 [KO:K11459]
121454151  Pcgf5; polycomb group RING finger protein 5 isoform X1 [KO:K11489]
121454801  Pcgf6; polycomb group RING finger protein 6 isoform X1 [KO:K11470]
121445713  LOW QUALITY PROTEIN: polycomb group RING finger protein 6-like [KO:K11470]
121465744  Pax6; paired box protein Pax-6 isoform X1 [KO:K08031]
121459733  Meis1; homeobox protein Meis1 isoform X1 [KO:K15613]
121457015  Hoxb1; homeobox protein Hox-B1 [KO:K09301]
121439248  Hoxd1; homeobox protein Hox-D1 [KO:K09301]
121439990  Hoxa1; homeobox protein Hox-A1 isoform X1 [KO:K09301]
121446383  Lhx5; LIM/homeobox protein Lhx5 [KO:K18493]
121459564  Otx1; homeobox protein OTX1 [KO:K09326]
121453158  Neurog1; neurogenin-1 [KO:K09081]
121444917  neurogenin-1-like [KO:K09081]
121456816  Hand1; heart- and neural crest derivatives-expressed protein 1 [KO:K09071]
121463461  Dlx5; homeobox protein DLX-5 [KO:K18489]
121464362  Myf5; myogenic factor 5 [KO:K18484]
121465930  Onecut1; hepatocyte nuclear factor 6 isoform X1 [KO:K08026]
121455945  Isl1; insulin gene enhancer protein ISL-1 [KO:K09370]
121447331  Zfhx3; zinc finger homeobox protein 3 [KO:K09378]
121437109  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
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
morg04010  MAPK signaling pathway
morg04151  PI3K-Akt signaling pathway
morg04310  Wnt signaling pathway
morg04350  TGF-beta signaling pathway
morg04630  JAK-STAT signaling pathway
KO pathway
ko04550   
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