Endoderm differentiation (WP2853)

Homo sapiens

Model depicting endoderm specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell lines, following differentiation to multiple lineages (ectoderm, mesoderm, endoderm, embryoid body). The underlying genomic data can be obtained from: https://www.synapse.org/#!Synapse:syn1773109 Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2853 CPTAC Assay Portal]


Nathan Salomonis , Egon Willighagen , Martina Summer-Kutmon , Kristina Hanspers , Alex Pico , Friederike Ehrhart , Susan Coort , and Eric Weitz


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Homo sapiens




Pathway Ontology

regulatory pathway


Label Type Compact URI Comment
STAT1 GeneProduct ensembl:ENSG00000115415
NANOG GeneProduct ensembl:ENSG00000111704
CDYL GeneProduct uniprot:Q9Y232
SFMBT1 GeneProduct uniprot:Q9UHJ3
UBR5 GeneProduct uniprot:O95071
SOX21 GeneProduct uniprot:Q9Y651
C1QBP GeneProduct uniprot:Q07021
BTAF1 GeneProduct uniprot:O14981
ZIC3 GeneProduct uniprot:O60481
PTHLH GeneProduct ensembl:ENSG00000087494
EPB41L5 GeneProduct ensembl:ENSG00000115109
LAMC1 GeneProduct ensembl:ENSG00000135862
PRDM14 GeneProduct ensembl:ENSG00000147596
SMAD3 GeneProduct ensembl:ENSG00000166949
NME1 GeneProduct uniprot:P15531
RTF1 GeneProduct ensembl:ENSG00000137815
RFX7 GeneProduct uniprot:Q2KHR2
TGFB1 GeneProduct ensembl:ENSG00000105329
NODAL GeneProduct ensembl:ENSG00000156574
RARG GeneProduct uniprot:P13631
BPTF GeneProduct ensembl:ENSG00000171634
TRIM71 GeneProduct uniprot:Q2Q1W2
SOX17 GeneProduct ensembl:ENSG00000164736
FOXN3 GeneProduct uniprot:O00409
GATA4 GeneProduct ensembl:ENSG00000136574
MBTD1 GeneProduct uniprot:Q05BQ5
HNF1B GeneProduct ensembl:ENSG00000275410
NAA15 GeneProduct uniprot:Q9BXJ9
PAX9 GeneProduct ensembl:ENSG00000198807
LRPPRC GeneProduct uniprot:P42704
LEO1 GeneProduct ensembl:ENSG00000166477
MBTD1 GeneProduct uniprot:Q05BQ5
OTX2 GeneProduct ensembl:ENSG00000165588
CTBP2 GeneProduct uniprot:P56545
CEBPZ GeneProduct uniprot:Q03701
DAB2 GeneProduct ensembl:ENSG00000153071
WWC1 GeneProduct uniprot:Q8IX03
DNMT3B GeneProduct uniprot:Q9UBC3
SFRP1 GeneProduct ensembl:ENSG00000104332
GDF3 GeneProduct ensembl:ENSG00000184344
WDHD1 GeneProduct uniprot:O75717
PBX1 GeneProduct uniprot:P40424
KDM4A GeneProduct uniprot:O75164
NOTCH1 GeneProduct ensembl:ENSG00000148400
SP4 GeneProduct uniprot:Q02446
HOXA1 GeneProduct ensembl:ENSG00000105991
EXT1 GeneProduct ensembl:ENSG00000182197
PAF1 GeneProduct ensembl:ENSG00000006712
JARID2 GeneProduct uniprot:Q92833
PABPC1 GeneProduct ensembl:ENSG00000070756
EOMES GeneProduct ensembl:ENSG00000163508
POU5F1 GeneProduct ensembl:ENSG00000204531
ONECUT1 GeneProduct ensembl:ENSG00000169856
TCF7L1 GeneProduct uniprot:Q9HCS4
FOXA1 GeneProduct ensembl:ENSG00000129514
NKX2-1 GeneProduct ensembl:ENSG00000136352
CTNNB1 GeneProduct ensembl:ENSG00000168036
TCF7 GeneProduct ensembl:ENSG00000081059
MIXL1 GeneProduct ensembl:ENSG00000185155
CTBP2 GeneProduct uniprot:P56545
ZNF462 GeneProduct uniprot:Q96JM2
CTR9 GeneProduct ensembl:ENSG00000198730
TAF4B GeneProduct uniprot:Q92750
DUSP5 GeneProduct ensembl:ENSG00000138166
SMAD4 GeneProduct ensembl:ENSG00000141646
ZFHX4 GeneProduct uniprot:Q86UP3
TAF5 GeneProduct uniprot:Q15542
WNT8A GeneProduct ensembl:ENSG00000061492
ELAVL1 GeneProduct ensembl:ENSG00000066044
MAD2L2 GeneProduct uniprot:Q9UI95
CER1 GeneProduct ensembl:ENSG00000147869
FOXA2 GeneProduct ensembl:ENSG00000125798
FOXO1 GeneProduct uniprot:Q12778
MTF2 GeneProduct uniprot:Q9Y483
DKK1 GeneProduct ensembl:ENSG00000107984
ZIC5 GeneProduct uniprot:Q96T25
PAX3 GeneProduct uniprot:P23760
APP GeneProduct ensembl:ENSG00000142192
AEBP2 GeneProduct uniprot:Q6ZN18
FOXN3 GeneProduct uniprot:O00409
TNRC6C GeneProduct ensembl:ENSG00000078687
BMPR1A GeneProduct ensembl:ENSG00000107779
TBX21 GeneProduct ensembl:ENSG00000073861
SMAD2 GeneProduct ensembl:ENSG00000175387
NCAPG2 GeneProduct uniprot:Q86XI2
CAND1 GeneProduct ensembl:ENSG00000111530
AEBP2 GeneProduct uniprot:Q6ZN18
BMP7 GeneProduct ensembl:ENSG00000101144
WWC1 GeneProduct uniprot:Q8IX03
SOX2 GeneProduct ensembl:ENSG00000181449
ASCC3 GeneProduct uniprot:Q8N3C0
AEBP2 GeneProduct uniprot:Q6ZN18
NOG GeneProduct ensembl:ENSG00000183691
ZBTB17 GeneProduct uniprot:Q13105
DUSP4 GeneProduct ensembl:ENSG00000120875
CDC73 GeneProduct ensembl:ENSG00000134371
ZNF281 GeneProduct uniprot:Q9Y2X9
LEF1 GeneProduct ensembl:ENSG00000138795
HOXC11 GeneProduct ensembl:ENSG00000123388
GRHL2 GeneProduct uniprot:Q6ISB3
TCEAL2 GeneProduct uniprot:Q9H3H9
HHEX GeneProduct ensembl:ENSG00000152804
SP4 GeneProduct uniprot:Q02446
GATA6 GeneProduct ensembl:ENSG00000141448
RARG GeneProduct uniprot:P13631
JARID2 GeneProduct ensembl:ENSG00000008083
TET1 GeneProduct uniprot:Q8NFU7
GLI2 GeneProduct uniprot:P10070
LHX1 GeneProduct ensembl:ENSG00000273706
MIR653 GeneProduct ensembl:ENSG00000199143
ELK4 GeneProduct uniprot:P28324
DIP2A GeneProduct uniprot:Q14689
PIAS1 GeneProduct uniprot:O75925
CRTC1 GeneProduct uniprot:Q6UUV9
AHDC1 GeneProduct uniprot:Q5TGY3
PBX3 GeneProduct uniprot:P40426
NLK GeneProduct uniprot:Q9UBE8
BCORL1 GeneProduct uniprot:Q5H9F3
ZFHX4 GeneProduct uniprot:Q86UP3
PLCH1 GeneProduct uniprot:Q4KWH8
WDFY2 GeneProduct uniprot:Q96P53
RARG GeneProduct uniprot:P13631
PARP8 GeneProduct uniprot:Q8N3A8
WDFY2 GeneProduct uniprot:Q96P53
GRHL2 GeneProduct uniprot:Q6ISB3
SESN1 GeneProduct uniprot:Q9Y6P5
RGS10 GeneProduct uniprot:O43665
CUL4B GeneProduct uniprot:Q13620
DDAH1 GeneProduct uniprot:O94760
SESN1 GeneProduct uniprot:Q9Y6P5
ASCC3 GeneProduct uniprot:Q8N3C0
ZNF462 GeneProduct uniprot:Q96JM2
NABP2 GeneProduct uniprot:Q9BQ15
PBX1 GeneProduct uniprot:P40424
ELP4 GeneProduct uniprot:Q96EB1
SCHIP1 GeneProduct uniprot:Q9P0W5
PLCH1 GeneProduct uniprot:Q4KWH8
PARP8 GeneProduct uniprot:Q8N3A8
TRIM5 GeneProduct uniprot:Q9C035
CEP250 GeneProduct uniprot:Q9BV73
PHF6 GeneProduct uniprot:Q8IWS0
ZNF462 GeneProduct uniprot:Q96JM2
HPRT1 GeneProduct uniprot:P00492
MBTD1 GeneProduct uniprot:Q05BQ5
PBX1 GeneProduct uniprot:P40424
TCF4 GeneProduct uniprot:P15884
TOX3 GeneProduct uniprot:O15405
SLC2A12 GeneProduct uniprot:Q8TD20
ACACA GeneProduct uniprot:Q13085
EMSY GeneProduct uniprot:Q7Z589
EMSY GeneProduct uniprot:Q7Z589
TOX GeneProduct uniprot:O94900
TRERF1 GeneProduct uniprot:Q96PN7
ATP8B2 GeneProduct uniprot:P98198
HPRT1 GeneProduct uniprot:P00492
TRERF1 GeneProduct uniprot:Q96PN7
VAV3 GeneProduct uniprot:Q9UKW4
TCF4 GeneProduct uniprot:P15884
MIR373 GeneProduct ensembl:ENSG00000199143
MIR375 GeneProduct ensembl:ENSG00000198973
MIR141 GeneProduct ensembl:ENSG00000207708
NR3C1 GeneProduct ensembl:ENSG00000113580
DUSP2 GeneProduct ensembl:ENSG00000158050
EZH2 GeneProduct ensembl:ENSG00000106462
FOXH1 GeneProduct ensembl:ENSG00000160973
SIAH2 GeneProduct ensembl:ENSG00000181788
RAB38 GeneProduct ensembl:ENSG00000123892
APC GeneProduct ensembl:ENSG00000134982
SOX7 GeneProduct ensembl:ENSG00000171056
MAP2K3 GeneProduct ensembl:ENSG00000034152
WNT3 GeneProduct ensembl:ENSG00000108379


  1. Sox7 plays crucial roles in parietal endoderm differentiation in F9 embryonal carcinoma cells through regulating Gata-4 and Gata-6 expression. Futaki S, Hayashi Y, Emoto T, Weber CN, Sekiguchi K. Mol Cell Biol. 2004 Dec;24(23):10492–503. PubMed Europe PMC Scholia
  2. Dkk1 and Wnt3 interact to control head morphogenesis in the mouse. Lewis SL, Khoo PL, De Young RA, Steiner K, Wilcock C, Mukhopadhyay M, et al. Development. 2008 May;135(10):1791–801. PubMed Europe PMC Scholia
  3. Repression of Wnt signaling by a Fer-type nonreceptor tyrosine kinase. Putzke AP, Rothman JH. Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16154–9. PubMed Europe PMC Scholia
  4. Chromatin and transcriptional signatures for Nodal signaling during endoderm formation in hESCs. Kim SW, Yoon SJ, Chuong E, Oyolu C, Wills AE, Gupta R, et al. Dev Biol. 2011 Sep 15;357(2):492–504. PubMed Europe PMC Scholia
  5. FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells. Sui L, Mfopou JK, Geens M, Sermon K, Bouwens L. Biochem Biophys Res Commun. 2012 Sep 28;426(3):380–5. PubMed Europe PMC Scholia
  6. MYC/MAX control ERK signaling and pluripotency by regulation of dual-specificity phosphatases 2 and 7. Chappell J, Sun Y, Singh A, Dalton S. Genes Dev. 2013 Apr 1;27(7):725–33. PubMed Europe PMC Scholia
  7. Siah ubiquitin ligases modulate nodal signaling during zebrafish embryonic development. Kang N, Won M, Rhee M, Ro H. Mol Cells. 2014 May;37(5):389–98. PubMed Europe PMC Scholia