KEGG   PATHWAY: ko04550Help
Entry
ko04550                     Pathway                                

Name
Signaling pathways regulating pluripotency of stem cells
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
BRITE hierarchy
Pathway map
ko04550  Signaling pathways regulating pluripotency of stem cells
ko04550

Ortholog table
Module
M00679  BMP signaling [PATH:ko04550]
M00681  Activin signaling [PATH:ko04550]
Disease
H01481  Myelodysplastic syndrome
H02151  Hereditary congenital facial paresis
Other DBs
BSID: 1033502
GO: 2000036
Orthology
K05419  leukemia inhibitory factor
K05058  leukemia inhibitory factor receptor
K05060  interleukin 6 signal transducer
K11217  Janus kinase 1 [EC:2.7.10.2]
K04447  Janus kinase 2 [EC:2.7.10.2]
K11218  Janus kinase 3 [EC:2.7.10.2]
K04692  signal transducer and activator of transcription 3
K17846  krueppel-like factor 4
K16796  transcription factor SOX2 (SOX group B)
K04377  Myc proto-oncogene protein
K04364  growth factor receptor-binding protein 2
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K10177  T-box protein 3
K10164  homeobox protein Nanog
K04667  inhibin beta A chain
K22687  inhibin beta B chain
K22688  inhibin beta C chain
K22689  inhibin beta E chain
K04666  nodal
K13567  activin receptor type-1B [EC:2.7.11.30]
K13568  activin receptor type-1C [EC:2.7.11.30]
K04670  activin receptor type-2A [EC:2.7.11.30]
K13596  activin receptor type-2B [EC:2.7.11.30]
K04500  mothers against decapentaplegic homolog 2/3
K04662  bone morphogenetic protein 4
K04673  bone morphogenetic protein receptor type-1A [EC:2.7.11.30]
K13578  bone morphogenetic protein receptor type-1B [EC:2.7.11.30]
K04675  activin receptor type-1 [EC:2.7.11.30]
K04671  bone morphogenetic protein receptor type-2 [EC:2.7.11.30]
K04676  mothers against decapentaplegic homolog 1
K16790  mothers against decapentaplegic homolog 5
K16791  mothers against decapentaplegic homolog 9
K04501  mothers against decapentaplegic homolog 4
K04680  DNA-binding protein inhibitor ID1
K17693  DNA-binding protein inhibitor ID2
K17694  DNA-binding protein inhibitor ID3
K17695  DNA-binding protein inhibitor ID4
K18498  dual specificity phosphatase 9 [EC:3.1.3.48 3.1.3.16]
K04441  p38 MAP kinase [EC:2.7.11.24]
K03209  wingless-type MMTV integration site family, member 1
K00182  wingless-type MMTV integration site family, member 2
K00312  wingless-type MMTV integration site family, member 3
K00408  wingless-type MMTV integration site family, member 4
K00444  wingless-type MMTV integration site family, member 5
K00445  wingless-type MMTV integration site family, member 6
K00572  wingless-type MMTV integration site family, member 7
K00714  wingless-type MMTV integration site family, member 8
K01064  wingless-type MMTV integration site family, member 9
K01357  wingless-type MMTV integration site family, member 10
K01384  wingless-type MMTV integration site family, member 11
K01558  wingless-type MMTV integration site family, member 16
K02432  frizzled 1/7
K02235  frizzled 2
K02329  frizzled 3
K02354  frizzled 4
K02375  frizzled 5/8
K02376  frizzled 6
K02842  frizzled 9/10
K02353  segment polarity protein dishevelled
K03083  glycogen synthase kinase 3 beta [EC:2.7.11.26]
K02157  axin 1
K04385  axin 2
K02085  adenomatosis polyposis coli protein
K02105  catenin beta 1
K09063  transcription factor E2-alpha
K08553  estrogen-related receptor beta
K08036  transcription factor 1, hepatocyte nuclear factor 1-alpha
K09367  POU domain transcription factor, class 5
K18497  fibroblast growth factor 2
K04362  fibroblast growth factor receptor 1 [EC:2.7.10.1]
K05093  fibroblast growth factor receptor 2 [EC:2.7.10.1]
K05094  fibroblast growth factor receptor 3 [EC:2.7.10.1]
K05095  fibroblast growth factor receptor 4 [EC:2.7.10.1]
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K05459  insulin-like growth factor 1
K05087  insulin-like growth factor 1 receptor [EC:2.7.10.1]
K09354  homeobox protein expressed in ES cells 1
K18487  zinc finger protein ZIC 3
K18499  Ski-like protein
K14439  SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 [EC:3.6.4.12]
K11305  histone acetyltransferase MYST3 [EC:2.3.1.48]
K11421  histone-lysine N-methyltransferase SETDB1 [EC:2.1.1.43]
K11478  protein Jumonji
K09222  RE1-silencing transcription factor
K11138  telomere-associated protein RIF1
K11487  polycomb group RING finger protein 1
K11460  polycomb group RING finger protein 2
K11488  polycomb group RING finger protein 3
K11459  polycomb group RING finger protein 4
K11489  polycomb group RING finger protein 5
K11470  polycomb group RING finger protein 6
K08031  paired box protein 6
K15613  homeobox protein Meis1
K18493  LIM homeobox protein 5
K09326  homeobox protein OTX1
K09081  neurogenin 1
K09071  heart-and neural crest derivatives-expressed protein 1
K18489  homeobox protein DLX5
K18484  myogenic factor 5
K08026  one cut domain, family member 1, hepatocyte nuclear factor 6
K09370  insulin gene enhancer protein ISL-1
K09378  AT-binding transcription factor 1
K18491  homeobox protein ESX1
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
LinkDB All DBs

DBGET integrated database retrieval system