Entry Name Signaling pathways regulating pluripotency of stem cells - Rattus norvegicus (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 - eukaryotesBRITE hierarchy
Pathway map rno04550 Signaling pathways regulating pluripotency of stem cells
Other DBs Organism Rattus norvegicus (rat) [GN:
rno ]
Gene 170911 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
171046 Tcf3; transcription factor E2-alpha isoform a [KO:K09063 ]
24205 Apc; adenomatous polyposis coli protein [KO:K02085 ]
24482 Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459 ]
25125 Stat3; signal transducer and activator of transcription 3 [KO:K04692 ]
25196 Inhbb; inhibin beta B chain precursor [KO:K22687 ]
25205 Il6st; interleukin-6 receptor subunit beta precursor [KO:K05060 ]
25261 Id1; DNA-binding protein inhibitor ID-1 [KO:K04680 ]
25296 Bmp4; bone morphogenetic protein 4 precursor [KO:K04662 ]
25513 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
25585 Id3; DNA-binding protein inhibitor ID-3 [KO:K17694 ]
25587 Id2; DNA-binding protein inhibitor ID-2 [KO:K17693 ]
25631 Smad3; mothers against decapentaplegic homolog 3 [KO:K23605 ]
25671 Smad1; mothers against decapentaplegic homolog 1 [KO:K04676 ]
25718 Igf1r; insulin-like growth factor 1 receptor isoform 2 precursor [KO:K05087 ] [EC:2.7.10.1 ]
287662 Pcgf2; polycomb group RING finger protein 2 [KO:K11460 ]
289316 Lefty2; left-right determination factor 2 precursor [KO:K04668 ]
29200 Inhba; inhibin beta A chain preproprotein [KO:K04667 ]
29357 Smad2; mothers against decapentaplegic homolog 2 [KO:K04500 ]
294562 Pou5f1; POU domain, class 5, transcription factor 1 [KO:K09367 ]
295602 Rif1; telomere-associated protein RIF1 isoform X1 [KO:K11138 ]
29741 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
299611 Apc2; adenomatous polyposis coli protein 2 [KO:K02085 ]
303251 Dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353 ]
303811 Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353 ]
305624 Pcgf3; polycomb group RING finger protein 3 [KO:K11488 ]
307829 Zfhx3; zinc finger homeobox protein 3 isoform X1 [KO:K09378 ]
309457 Pcgf6; polycomb group RING finger protein 6 [KO:K11470 ]
312398 Smarcad1; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 [KO:K14439 ] [EC:5.6.2.-]
312480 Pcgf1; polycomb group RING finger protein 1 [KO:K11487 ]
366508 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
367858 Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833 ]
498299 Lefty1; left-right determination factor 1 precursor [KO:K04668 ]
50554 Smad4; mothers against decapentaplegic homolog 4 [KO:K04501 ]
58960 Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369 ] [EC:2.7.12.2 ]
59112 Hand1; heart- and neural crest derivatives-expressed protein 1 [KO:K09071 ]
59328 Smad5; mothers against decapentaplegic homolog 5 [KO:K16790 ]
60584 Lif; leukemia inhibitory factor precursor [KO:K05419 ]
60664 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
64444 Isl1; insulin gene enhancer protein ISL-1 [KO:K09370 ]
64549 Inhbc; inhibin beta C chain precursor [KO:K22688 ]
681178 Pcgf5; polycomb group RING finger protein 5 [KO:K11489 ]
681740 Jarid2; jumonji and AT-rich interaction domain containing 2 [KO:K11478 ]
81504 Grb2; growth factor receptor-bound protein 2 [KO:K04364 ]
81680 Lifr; leukemia inhibitory factor receptor precursor [KO:K05058 ]
83618 Rest; RE1-silencing transcription factor [KO:K09222 ]
83711 Inhbe; inhibin beta E chain precursor [KO:K22689 ]
83721 Dvl1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353 ]
85243 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
85435 Smad9; mothers against decapentaplegic homolog 9 [KO:K16791 ]
Reference Authors Bhartiya D, Lenka N (ed).
Title Pluripotent Stem Cells
Journal Reference Authors Hassani SN, Totonchi M, Gourabi H, Scholer HR, Baharvand H
Title Signaling roadmap modulating naive and primed pluripotency.
Journal Reference Authors Jaenisch R, Young R
Title Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming.
Journal Reference Authors Zhang H, Wang ZZ
Title Mechanisms that mediate stem cell self-renewal and differentiation.
Journal Reference Authors Itoh F, Watabe T, Miyazono K
Title Roles of TGF-beta family signals in the fate determination of pluripotent stem cells.
Journal Reference Authors Saunders A, Faiola F, Wang J
Title Concise review: pursuing self-renewal and pluripotency with the stem cell factor Nanog.
Journal 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 Reference Authors Okita K, Yamanaka S
Title Intracellular signaling pathways regulating pluripotency of embryonic stem cells.
Journal 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 Reference Authors Nakai-Futatsugi Y, Niwa H
Title Transcription factor network in embryonic stem cells: heterogeneity under the stringency.
Journal 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 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 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 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 Reference Authors Sui L, Bouwens L, Mfopou JK
Title Signaling pathways during maintenance and definitive endoderm differentiation of embryonic stem cells.
Journal Reference Authors Do JT, Scholer HR
Title Regulatory circuits underlying pluripotency and reprogramming.
Journal Reference Authors Pan G, Thomson JA
Title Nanog and transcriptional networks in embryonic stem cell pluripotency.
Journal 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 Reference Authors Loh YH, Ng JH, Ng HH
Title Molecular framework underlying pluripotency.
Journal Reference Authors Greenow K, Clarke AR
Title Controlling the stem cell compartment and regeneration in vivo: the role of pluripotency pathways.
Journal Related KO pathway 
