KEGG   PATHWAY: dsp04550
Entry
dsp04550                    Pathway                                
Name
Signaling pathways regulating pluripotency of stem cells - Dipodomys spectabilis (banner-tailed kangaroo rat)
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
dsp04550  Signaling pathways regulating pluripotency of stem cells
dsp04550

Other DBs
GO: 2000036
Organism
Dipodomys spectabilis (banner-tailed kangaroo rat) [GN:dsp]
Gene
122097190  Lif; leukemia inhibitory factor [KO:K05419]
122116935  Lifr; leukemia inhibitory factor receptor isoform X1 [KO:K05058]
122117279  Il6st; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
122110980  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
122124653  Jak2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
122100890  Jak3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
122103310  Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
122123229  Klf4; Krueppel-like factor 4 [KO:K17846]
122125089  Sox2; transcription factor SOX-2 [KO:K16796]
122102408  Myc; myc proto-oncogene protein [KO:K04377]
122128376  Grb2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
122114391  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
122099331  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
122095844  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122096287  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
122095294  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122121501  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122107232  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122123339  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform-like [KO:K00922] [EC:2.7.1.153]
122108047  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
122100872  Pik3r2; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122117343  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122097416  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122101263  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122126696  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122101281  Tbx3; T-box transcription factor TBX3 [KO:K10177]
122128230  LOW QUALITY PROTEIN: putative homeobox protein NANOG2 [KO:K10164]
122120886  Inhba; LOW QUALITY PROTEIN: inhibin beta A chain [KO:K04667]
122112415  Inhbb; inhibin beta B chain [KO:K22687]
122124021  Inhbc; inhibin beta C chain [KO:K22688]
122124343  Inhbe; inhibin beta E chain [KO:K22689]
122122223  Nodal; nodal homolog [KO:K04666]
122098383  Acvr1b; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
122110815  Acvr1c; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
122110790  Acvr2a; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
122096745  Acvr2b; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
122104270  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
122114693  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
122110043  Bmp4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
122116497  Bmpr1a; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
122127136  Bmpr1b; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
122110801  Acvr1; LOW QUALITY PROTEIN: activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
122096406  Bmpr2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
122127188  Smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
122100913  Smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
122112702  Smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
122104309  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
122120303  Id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
122108785  Id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
122115201  Id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
122107002  Id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
122097078  Dusp9; dual specificity protein phosphatase 9 [KO:K18498] [EC:3.1.3.16 3.1.3.48]
122111502  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
122111503  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
122123649  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
122106358  Wnt1; proto-oncogene Wnt-1 [KO:K03209]
122104095  Wnt2b; protein Wnt-2b [KO:K00182]
122121825  Wnt2; protein Wnt-2 [KO:K00182]
122103469  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
122098964  Wnt3a; protein Wnt-3a [KO:K00312]
122115226  Wnt4; protein Wnt-4 [KO:K00408]
122099575  Wnt5b; LOW QUALITY PROTEIN: protein Wnt-5b [KO:K00444]
122108141  Wnt5a; protein Wnt-5a isoform X1 [KO:K00444]
122107573  Wnt6; protein Wnt-6 [KO:K00445]
122096831  Wnt7b; protein Wnt-7b [KO:K00572]
122108198  Wnt7a; protein Wnt-7a [KO:K00572]
122115988  Wnt8b; protein Wnt-8b [KO:K00714]
122118246  Wnt8a; protein Wnt-8a [KO:K00714]
122103516  Wnt9b; protein Wnt-9b [KO:K01064]
122098938  Wnt9a; LOW QUALITY PROTEIN: protein Wnt-9a [KO:K01064]
122106350  Wnt10b; protein Wnt-10b [KO:K01357]
122107497  Wnt10a; protein Wnt-10a [KO:K01357]
122115365  Wnt11; protein Wnt-11 isoform X1 [KO:K01384]
122121786  Wnt16; protein Wnt-16 [KO:K01558]
122096462  Fzd7; frizzled-7 [KO:K02432]
122111920  Fzd1; frizzled-1 [KO:K02432]
122103290  Fzd2; frizzled-2 [KO:K02235]
122125249  Fzd3; frizzled-3 isoform X1 [KO:K02329]
122114819  Fzd4; frizzled-4 [KO:K02354]
122113306  Fzd8; frizzled-8 [KO:K02375]
122107578  Fzd5; frizzled-5 [KO:K02375]
122102404  Fzd6; frizzled-6 [KO:K02376]
122113827  Fzd9; frizzled-9 [KO:K02842]
122098849  Fzd10; frizzled-10 [KO:K02842]
122127322  Dvl1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
122096769  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
122100418  Dvl2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
122096813  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
122098148  Axin1; axin-1 isoform X1 [KO:K02157]
122094958  Axin2; axin-2 [KO:K04385]
122122822  Apc2; LOW QUALITY PROTEIN: adenomatous polyposis coli protein 2 [KO:K02085]
122118219  Apc; adenomatous polyposis coli protein isoform X1 [KO:K02085]
122124883  Ctnnb1; catenin beta-1 [KO:K02105]
122122778  Tcf3; transcription factor E2-alpha isoform X1 [KO:K09063]
122118862  Esrrb; steroid hormone receptor ERR2 isoform X1 [KO:K08553]
122115432  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
122111327  Pou5f1; POU domain, class 5, transcription factor 1 isoform X1 [KO:K09367]
122119078  Fgf2; fibroblast growth factor 2 [KO:K18497]
122107616  Fgfr1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
122126852  Fgfr2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
122100692  Fgfr3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
122096494  Fgfr4; fibroblast growth factor receptor 4 isoform X1 [KO:K05095] [EC:2.7.10.1]
122095011  Hras; GTPase HRas isoform X1 [KO:K02833]
122098841  Kras; GTPase KRas isoform X1 [KO:K07827]
122118367  Nras; GTPase NRas [KO:K07828]
122107826  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
122119198  Igf1; insulin-like growth factor I isoform X1 [KO:K05459]
122123999  Igf1r; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
122108241  Hesx1; homeobox expressed in ES cells 1 [KO:K09354]
122097111  Zic3; zinc finger protein ZIC 3 isoform X1 [KO:K18487]
122126732  LOW QUALITY PROTEIN: left-right determination factor 2-like [KO:K04668]
122107235  Skil; ski-like protein [KO:K18499]
122127125  Smarcad1; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 [KO:K14439] [EC:5.6.2.-]
122107613  Kat6a; histone acetyltransferase KAT6A isoform X1 [KO:K11305] [EC:2.3.1.48]
122109123  Setdb1; histone-lysine N-methyltransferase SETDB1 isoform X1 [KO:K11421] [EC:2.1.1.366]
122106977  Jarid2; protein Jumonji isoform X1 [KO:K11478]
122106774  Rest; RE1-silencing transcription factor [KO:K09222]
122110740  Rif1; telomere-associated protein RIF1 isoform X1 [KO:K11138]
122125181  Pcgf1; polycomb group RING finger protein 1 [KO:K11487]
122103517  Pcgf2; polycomb group RING finger protein 2 isoform X1 [KO:K11460]
122102202  Pcgf3; polycomb group RING finger protein 3 [KO:K11488]
122113043  Bmi1; polycomb complex protein BMI-1 [KO:K11459]
122115796  Pcgf5; polycomb group RING finger protein 5 isoform X1 [KO:K11489]
122115964  Pcgf6; polycomb group RING finger protein 6 isoform X1 [KO:K11470]
122117686  Pax6; paired box protein Pax-6 isoform X1 [KO:K08031]
122117485  Meis1; homeobox protein Meis1 isoform X1 [KO:K15613]
122103429  Hoxb1; homeobox protein Hox-B1 [KO:K09301]
122112178  Hoxa1; homeobox protein Hox-A1 [KO:K09301]
122120120  Hoxd1; homeobox protein Hox-D1 [KO:K09301]
122098591  Lhx5; LIM/homeobox protein Lhx5 [KO:K18493]
122117500  Otx1; homeobox protein OTX1 isoform X1 [KO:K09326]
122100930  Neurog1; neurogenin-1 [KO:K09081]
122118572  Hand1; heart- and neural crest derivatives-expressed protein 1 [KO:K09071]
122111932  Dlx5; homeobox protein DLX-5 [KO:K18489]
122124404  Myf5; myogenic factor 5 [KO:K18484]
122114677  Onecut1; hepatocyte nuclear factor 6 [KO:K08026]
122116995  Isl1; insulin gene enhancer protein ISL-1 isoform X1 [KO:K09370]
122126174  Zfhx3; 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
dsp04010  MAPK signaling pathway
dsp04151  PI3K-Akt signaling pathway
dsp04310  Wnt signaling pathway
dsp04350  TGF-beta signaling pathway
dsp04630  JAK-STAT signaling pathway
KO pathway
ko04550   
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