metaid_0000021
constant: true
value: 5.0
name: k3c
type: Parameter

BIOMD0000000204
units def: metaid_0000058
parameter: metaid_0000027
occurs in: http://identifiers.org/taxonomy/9606
substance units: metaid_0000058
parameter: metaid_0000007
reaction: metaid_0000048
parameter: metaid_0000032
parameter: metaid_0000012
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Vijayalakshmi
    family: Chelliah
parameter: metaid_0000020
time units: metaid_0000060
parameter: metaid_0000018
notes: Chickarmane2006 - Stem cell switch irreversible Kinetic modeling approach of the transcriptional dynamics of the embryonic stem cell switch. This model is described in the article: Transcriptional dynamics of the embryonic stem cell switch. Chickarmane V, Troein C, Nuber UA, Sauro HM, Peterson C PLoS Computational Biology. 2006; 2(9):e123 Abstract: Recent ChIP experiments of human and mouse embryonic stem cells have elucidated the architecture of the transcriptional regulatory circuitry responsible for cell determination, which involves the transcription factors OCT4, SOX2, and NANOG. In addition to regulating each other through feedback loops, these genes also regulate downstream target genes involved in the maintenance and differentiation of embryonic stem cells. A search for the OCT4-SOX2-NANOG network motif in other species reveals that it is unique to mammals. With a kinetic modeling approach, we ascribe function to the observed OCT4-SOX2-NANOG network by making plausible assumptions about the interactions between the transcription factors at the gene promoter binding sites and RNA polymerase (RNAP), at each of the three genes as well as at the target genes. We identify a bistable switch in the network, which arises due to several positive feedback loops, and is switched on/off by input environmental signals. The switch stabilizes the expression levels of the three genes, and through their regulatory roles on the downstream target genes, leads to a binary decision: when OCT4, SOX2, and NANOG are expressed and the switch is on, the self-renewal genes are on and the differentiation genes are off. The opposite holds when the switch is off. The model is extremely robust to parameter changes. In addition to providing a self-consistent picture of the transcriptional circuit, the model generates several predictions. Increasing the binding strength of NANOG to OCT4 and SOX2, or increasing its basal transcriptional rate, leads to an irreversible bistable switch: the swi…
parameter: metaid_0000015
reaction: metaid_0000050
reaction: metaid_0000054
parameter: metaid_0000023
parameter: metaid_0000003
creator:
  ORG:
    orgname: Keck Graduate Institute, California
  n:
    given: Vijay
    family: Chickarmane
species: metaid_0000043
is version of: GO:0048863
reaction: metaid_0000057
species: metaid_0000044
curated: true
parameter: metaid_0000026
parameter: metaid_0000006
created:
  W3 CDTF: Wed Nov 26 13:10:43 GMT 2008
parameter: metaid_0000031
area units: metaid_0000005
parameter: metaid_0000011
parameter: metaid_0000009
is: MODEL7957942740
parameter: metaid_0000030
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Lukas
    family: Endler
parameter: metaid_0000034
parameter: metaid_0000014
species: metaid_0000046
reaction: metaid_0000053
parameter: metaid_0000022
occurs in: http://identifiers.org/taxonomy/10090
reaction: metaid_0000052
compartment: metaid_0000035
reaction: metaid_0000056
parameter: metaid_0000025
creator:
  ORG:
    orgname: Lund Strategic Research Centre for Stem Cell Biology and Cell Therapy, Lund University, Sweden.
  n:
    given: Carsten
    family: Peterson
parameter: metaid_0000005
modified:
  W3 CDTF: Wed Jun 05 17:57:58 BST 2013
parameter: metaid_0000029
species: metaid_0000036
species: metaid_0000045
volume units: metaid_0000059
species: metaid_0000037
units def: metaid_0000060
parameter: metaid_0000010
parameter: metaid_0000008
reaction: metaid_0000049
length unit: length
species: metaid_0000040
parameter: metaid_0000033
parameter: metaid_0000013
parameter: metaid_0000017
parameter: metaid_0000021
species: metaid_0000047
species: metaid_0000038
type: SBMLModel
parameter: metaid_0000019
name: Chickarmane2006 - Stem cell switch irreversible
parameter: metaid_0000016
reaction: metaid_0000051
species: metaid_0000039
reaction: metaid_0000055
species: metaid_0000042
is described by: http://identifiers.org/pubmed/16978048
species: metaid_0000041
parameter: metaid_0000024
units def: metaid_0000059
parameter: metaid_0000004
parameter: metaid_0000028

metaid_0000011
constant: true
value: 1.0
name: gamma1
type: Parameter

147793
stoichiometry: 1.0
species: metaid_0000044
type: SpeciesReference

147522
exponent: 1.0
scale: 0
multipler: 1.0
kind: DIMENSIONLESS
type: SBMLUnit

metaid_0000046
has part: Q6ZRP7
has part: Q01860
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.1
initial amount: NaN
in compartment: metaid_0000035
type: Species

metaid_0000051
kinetic law: 147769
product: 147756
reactant: 147743
is version of: GO:0030163
fast: false
reversible: false
type: Reaction

metaid_0000031
constant: true
value: 1.0E-4
name: eta7
type: Parameter

metaid_0000030
constant: true
value: 0.1
name: g1
type: Parameter

147805
stoichiometry: 1.0
species: metaid_0000046
type: SpeciesReference

metaid_0000039
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: metaid_0000035
type: Species

147950
stoichiometry: 1.0
species: metaid_0000040
type: SpeciesReference

metaid_0000029
constant: true
value: 1.0
name: gamma3
type: Parameter

metaid_0000006
constant: true
value: 0.5
name: a3
type: Parameter

147938
stoichiometry: 1.0
species: metaid_0000044
type: SpeciesReference

metaid_0000020
constant: true
value: 0.001
name: k2c
type: Parameter

metaid_0000010
constant: true
value: 0.001
name: b3
type: Parameter

metaid_0000047
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000035
type: Species

metaid_0000052
kinetic law: 147817
product: 147805
reactant: 147793
reactant: 147781
is version of: GO:0006461
fast: false
reversible: false
type: Reaction

147573
stoichiometry: 1.0
species: metaid_0000043
type: SpeciesReference

metaid_0000053
kinetic law: 147853
product: 147841
reactant: 147829
is version of: GO:0030163
fast: false
reversible: false
type: Reaction

148034
stoichiometry: 1.0
species: metaid_0000047
type: SpeciesReference

metaid_0000038
encodes: Q6ZRP7
is version of: ENSG00000165661
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000035
type: Species

metaid_0000007
constant: true
value: 1000.0
name: f
type: Parameter

metaid_0000028
constant: true
value: 0.001
name: d3
type: Parameter

metaid_0000058
unit: 147522
name: arb_substance
type: SBMLUnitsDef

metaid_0000013
constant: true
value: 0.01
name: e1
type: Parameter

metaid_0000033
constant: true
value: 1.0
name: h2
type: Parameter

metaid_0000060
unit: 147547
name: arb_time
type: SBMLUnitsDef

metaid_0000048
kinetic law: 147626
is version of: GO:0010467
fast: false
reversible: false
modifier: 147586
reactant: 147560
type: Reaction
modifier: 147599
product: 147573
modifier: 147613

147781
stoichiometry: 1.0
species: metaid_0000043
type: SpeciesReference

metaid_0000027
constant: true
value: 0.001
name: d2
type: Parameter

147560
stoichiometry: 1.0
species: metaid_0000036
type: SpeciesReference

metaid_0000008
constant: true
value: 0.0011
name: b1
type: Parameter

metaid_0000059
unit: 147535
name: arb_volume
type: SBMLUnitsDef

metaid_0000012
constant: true
value: 1.0E-4
name: eta5
type: Parameter

metaid_0000040
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000035
type: Species

metaid_0000032
constant: true
value: 0.0011
name: h1
type: Parameter

metaid_0000050
kinetic law: 147730
modifier: 147704
fast: false
product: 147691
reversible: false
reactant: 147678
type: Reaction
is version of: GO:0010467
modifier: 147717

metaid_0000049
kinetic law: 147665
product: 147652
reactant: 147639
is version of: GO:0030163
fast: false
reversible: false
type: Reaction

metaid_0000026
constant: true
value: 0.0011
name: d1
type: Parameter

147756
stoichiometry: 1.0
species: metaid_0000040
type: SpeciesReference

metaid_0000009
constant: true
value: 0.001
name: b2
type: Parameter

148046
stoichiometry: 1.0
species: metaid_0000040
type: SpeciesReference

147841
stoichiometry: 1.0
species: metaid_0000040
type: SpeciesReference

147691
stoichiometry: 1.0
species: metaid_0000045
type: SpeciesReference

metaid_0000005
constant: true
value: 0.01
name: a2
type: Parameter

metaid_0000041
is version of: P04637
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000035
type: Species

147974
stoichiometry: 1.0
species: metaid_0000039
type: SpeciesReference

metaid_0000015
constant: true
value: 0.001
name: f2
type: Parameter

metaid_0000035
is version of: GO:0005623
constant: true
size: 1.0
spatial dimensions: 3.0
type: Compartment

metaid_0000042
constant: false
boundary condition: true
has only substance units: false
initial concentration: 10.0
initial amount: NaN
in compartment: metaid_0000035
type: Species

metaid_0000056
reactant: 147974
fast: false
kinetic law: 148022
reversible: false
modifier: 148010
is version of: GO:0010467
product: 147986
modifier: 147998
type: Reaction

metaid_0000025
constant: true
value: 0.5
name: c3
type: Parameter

metaid_0000004
constant: true
value: 1.0
name: a1
type: Parameter

147829
stoichiometry: 1.0
species: metaid_0000046
type: SpeciesReference

147547
exponent: 1.0
scale: 0
multipler: 1.0
kind: DIMENSIONLESS
type: SBMLUnit

147877
stoichiometry: 1.0
species: metaid_0000044
type: SpeciesReference

metaid_0000014
constant: true
value: 0.1
name: e2
type: Parameter

147639
stoichiometry: 1.0
species: metaid_0000043
type: SpeciesReference

metaid_0000043
is version of: Q01860
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: metaid_0000035
type: Species

metaid_0000034
constant: true
value: 0.01
name: gamma4
type: Parameter

metaid_0000057
kinetic law: 148058
product: 148046
reactant: 148034
is version of: GO:0030163
fast: false
reversible: false
type: Reaction

metaid_0000024
constant: true
value: 0.01
name: c2
type: Parameter

metaid_0000003
constant: true
value: 1.0E-4
name: eta1
type: Parameter

metaid_0000017
constant: true
value: 0.05
name: f3
type: Parameter

metaid_0000018
constant: true
value: 1.0
name: gamma2
type: Parameter

147986
stoichiometry: 1.0
species: metaid_0000047
type: SpeciesReference

metaid_0000044
is version of: Q6ZRP7
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: metaid_0000035
type: Species

metaid_0000037
is version of: ENSG00000176654
encodes: Q8N7R0
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000035
type: Species

147743
stoichiometry: 1.0
species: metaid_0000045
type: SpeciesReference

147652
stoichiometry: 1.0
species: metaid_0000040
type: SpeciesReference

metaid_0000023
constant: true
value: 1.0
name: c1
type: Parameter

metaid_0000054
type: Reaction
modifier: 147889
fast: false
reversible: false
reactant: 147865
is version of: GO:0010467
kinetic law: 147926
modifier: 147914
product: 147877
modifier: 147901

metaid_0000019
constant: true
value: 0.05
name: k1c
type: Parameter

metaid_0000016
constant: true
value: 0.001
name: f1
type: Parameter

metaid_0000045
is version of: Q8N7R0
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: metaid_0000035
type: Species

metaid_0000036
encodes: Q01860
is version of: ENSG00000204531
constant: false
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000035
type: Species

147678
stoichiometry: 1.0
species: metaid_0000037
type: SpeciesReference

metaid_0000022
constant: true
value: 1.0E-4
name: eta3
type: Parameter

147865
stoichiometry: 1.0
species: metaid_0000038
type: SpeciesReference

metaid_0000055
kinetic law: 147962
product: 147950
reactant: 147938
is version of: GO:0030163
fast: false
reversible: false
type: Reaction

147535
exponent: 1.0
scale: 0
multipler: 1.0
kind: DIMENSIONLESS
type: SBMLUnit