Mesodermal commitment pathway (WP2857)

Homo sapiens

Model depicting mesodermal 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:!Synapse:syn1773109. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


Nathan Salomonis , Kristina Hanspers , Mshel016 , Martina Summer-Kutmon , Elisa Cirillo , Egon Willighagen , Marvin Martens , and Eric Weitz


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Homo sapiens



Pathway Ontology

regulatory pathway


Label Type Compact Identifier Comment
PIAS1 GeneProduct ensembl:ENSG00000033800
NLK GeneProduct ensembl:ENSG00000087095
BCORL1 GeneProduct ensembl:ENSG00000085185
DIP2A GeneProduct ensembl:ENSG00000160305
AHDC1 GeneProduct ensembl:ENSG00000126705
CRTC1 GeneProduct ensembl:ENSG00000105662
ELK4 GeneProduct ensembl:ENSG00000158711
PBX3 GeneProduct ensembl:ENSG00000167081
ZFHX4 GeneProduct ensembl:ENSG00000091656
PLCH1 GeneProduct ensembl:ENSG00000114805
WDFY2 GeneProduct ensembl:ENSG00000139668
C2orf44 GeneProduct ensembl:ENSG00000163026
PRKACA GeneProduct ensembl:ENSG00000072062
EOMES GeneProduct ensembl:ENSG00000163508
NOG GeneProduct ensembl:ENSG00000183691
GDF3 GeneProduct ensembl:ENSG00000184344
RARG GeneProduct ensembl:ENSG00000172819
PARP8 GeneProduct ensembl:ENSG00000151883
TEAD2 GeneProduct ensembl:ENSG00000074219
NODAL GeneProduct ensembl:ENSG00000156574
WDFY2 GeneProduct ensembl:ENSG00000139668
GRHL2 GeneProduct ensembl:ENSG00000083307
HES7 GeneProduct ensembl:ENSG00000179111
SMAD1 GeneProduct ensembl:ENSG00000170365
SESN1 GeneProduct ensembl:ENSG00000080546
RGS10 GeneProduct ensembl:ENSG00000148908
SMAD3 GeneProduct ensembl:ENSG00000166949
FOXC1 GeneProduct ensembl:ENSG00000054598
KLF5 GeneProduct ensembl:ENSG00000102554
JAK2 GeneProduct ensembl:ENSG00000096968
ZIC2 GeneProduct ensembl:ENSG00000043355
CSRP2 GeneProduct ensembl:ENSG00000175183
CUL4B GeneProduct ensembl:ENSG00000158290
SMAD4 GeneProduct ensembl:ENSG00000141646
DLL1 GeneProduct ensembl:ENSG00000198719
YAP1 GeneProduct ensembl:ENSG00000137693
EXT1 GeneProduct ensembl:ENSG00000182197
DDAH1 GeneProduct ensembl:ENSG00000153904
SESN1 GeneProduct ensembl:ENSG00000080546
TRIM28 GeneProduct ensembl:ENSG00000130726
ATP8B2 GeneProduct ensembl:ENSG00000143515
CCND1 GeneProduct ensembl:ENSG00000110092
PAX6 GeneProduct ensembl:ENSG00000007372
ASCC3 GeneProduct ensembl:ENSG00000112249
ZNF462 GeneProduct ensembl:ENSG00000148143
NABP2 GeneProduct ensembl:ENSG00000139579
MEIS1 GeneProduct ensembl:ENSG00000143995
BMP4 GeneProduct ensembl:ENSG00000125378
MIR302C GeneProduct ensembl:ENSG00000199102
HTT GeneProduct ensembl:ENSG00000197386
TEAD1 GeneProduct ensembl:ENSG00000187079
BMPR2 GeneProduct ensembl:ENSG00000204217
CEP250 GeneProduct ensembl:ENSG00000126001
C11orf30 GeneProduct ensembl:ENSG00000158636
MACF1 GeneProduct ensembl:ENSG00000127603
PBX1 GeneProduct ensembl:ENSG00000185630
ARID5B GeneProduct ensembl:ENSG00000150347
TBX6 GeneProduct ensembl:ENSG00000149922
CCDC6 GeneProduct ensembl:ENSG00000108091
ELP4 GeneProduct ensembl:ENSG00000109911
ASCC3 GeneProduct ensembl:ENSG00000112249
ACVR2A GeneProduct ensembl:ENSG00000121989
SCHIP1 GeneProduct ensembl:ENSG00000151967
HNF4A GeneProduct ensembl:ENSG00000101076
ADAM19 GeneProduct ensembl:ENSG00000135074
PLCH1 GeneProduct ensembl:ENSG00000114805
C9orf72 GeneProduct ensembl:ENSG00000147894
TBX3 GeneProduct ensembl:ENSG00000135111
PARP8 GeneProduct ensembl:ENSG00000151883
GATA6 GeneProduct ensembl:ENSG00000141448
TRIM5 GeneProduct ensembl:ENSG00000132256
SMAD6 GeneProduct ensembl:ENSG00000137834
WNT3A GeneProduct ensembl:ENSG00000154342
FOXC1 GeneProduct ensembl:ENSG00000054598
CEP250 GeneProduct ensembl:ENSG00000126001
TCF7L1 GeneProduct ensembl:ENSG00000152284
PHF6 GeneProduct ensembl:ENSG00000156531
ZNF462 GeneProduct ensembl:ENSG00000148143
FGFR1 GeneProduct ensembl:ENSG00000077782
LATS1 GeneProduct ensembl:ENSG00000131023
TBX1 GeneProduct ensembl:ENSG00000184058
CCDC88A GeneProduct ensembl:ENSG00000115355
KDM6A GeneProduct ensembl:ENSG00000147050
AXIN1 GeneProduct ensembl:ENSG00000103126
HPRT1 GeneProduct ensembl:ENSG00000165704
ARL4A GeneProduct ensembl:ENSG00000122644
EPB41L5 GeneProduct ensembl:ENSG00000115109
MBTD1 GeneProduct ensembl:ENSG00000011258
PBX1 GeneProduct ensembl:ENSG00000185630
BMP7 GeneProduct ensembl:ENSG00000101144
ACVR2B GeneProduct ensembl:ENSG00000114739
NANOG GeneProduct ensembl:ENSG00000111704
FOXA1 GeneProduct ensembl:ENSG00000129514
TCF4 GeneProduct ensembl:ENSG00000196628
SNAI1 GeneProduct ensembl:ENSG00000124216
FOXA2 GeneProduct ensembl:ENSG00000125798
TOX3 GeneProduct ensembl:ENSG00000103460
POU5F1 GeneProduct ensembl:ENSG00000204531
CSRP2 GeneProduct ensembl:ENSG00000175183
MIXL1 GeneProduct ensembl:ENSG00000185155
RPL38 GeneProduct ensembl:ENSG00000172809
SLC2A12 GeneProduct ensembl:ENSG00000146411
ARL4A GeneProduct ensembl:ENSG00000122644
FOXH1 GeneProduct ensembl:ENSG00000160973
PITX2 GeneProduct ensembl:ENSG00000164093
CHRD GeneProduct ensembl:ENSG00000090539
FOXC2 GeneProduct ensembl:ENSG00000176692
WNT3 GeneProduct ensembl:ENSG00000108379
ACACA GeneProduct ensembl:ENSG00000278540
C11orf30 GeneProduct ensembl:ENSG00000158636
KLF4 GeneProduct ensembl:ENSG00000136826
C11orf30 GeneProduct ensembl:ENSG00000158636
SETD2 GeneProduct ensembl:ENSG00000181555
BMPR1A GeneProduct ensembl:ENSG00000107779
TOX GeneProduct ensembl:ENSG00000198846
INHBA GeneProduct ensembl:ENSG00000122641
TRERF1 GeneProduct ensembl:ENSG00000124496
CCND1 GeneProduct ensembl:ENSG00000110092
C6orf201 GeneProduct ensembl:ENSG00000185689
SOX2 GeneProduct ensembl:ENSG00000181449
MSGN1 GeneProduct ensembl:ENSG00000151379
LEF1 GeneProduct ensembl:ENSG00000138795
PRKAR1A GeneProduct ensembl:ENSG00000108946
HMGA2 GeneProduct ensembl:ENSG00000149948
SRF GeneProduct ensembl:ENSG00000112658
TWSG1 GeneProduct ensembl:ENSG00000128791
FOXA2 GeneProduct ensembl:ENSG00000125798
HAND1 GeneProduct ensembl:ENSG00000113196
PPP2CA GeneProduct ensembl:ENSG00000113575
ATP8B2 GeneProduct ensembl:ENSG00000143515
HPRT1 GeneProduct ensembl:ENSG00000165704
ACVR1 GeneProduct ensembl:ENSG00000115170
SMAD2 GeneProduct ensembl:ENSG00000175387
DKK1 GeneProduct ensembl:ENSG00000107984
EXT2 GeneProduct ensembl:ENSG00000151348
RARB GeneProduct ensembl:ENSG00000077092
LEFTY1 GeneProduct ensembl:ENSG00000243709
BHLHE40 GeneProduct ensembl:ENSG00000134107
TRERF1 GeneProduct ensembl:ENSG00000124496
VAV3 GeneProduct ensembl:ENSG00000134215
TCF4 GeneProduct ensembl:ENSG00000196628
AMH GeneProduct ensembl:ENSG00000104899
GATA3 GeneProduct ensembl:ENSG00000107485
SOX17 GeneProduct ensembl:ENSG00000164736
LEFTY2 GeneProduct ensembl:ENSG00000143768
NANOG GeneProduct ensembl:ENSG00000111704
FZD4 GeneProduct ensembl:ENSG00000174804
FZD5 GeneProduct ensembl:ENSG00000163251
FZD8 GeneProduct ensembl:ENSG00000177283
FGF8 GeneProduct ensembl:ENSG00000107831
AXIN2 GeneProduct ensembl:ENSG00000168646
NFE2L2 GeneProduct ensembl:ENSG00000116044
SOX2 GeneProduct ensembl:ENSG00000181449
UBR5 GeneProduct ensembl:ENSG00000104517
SOX21 GeneProduct ensembl:ENSG00000125285
C1QBP GeneProduct ensembl:ENSG00000108561
ZIC3 GeneProduct ensembl:ENSG00000156925
TRIM71 GeneProduct ensembl:ENSG00000206557
DNMT3B GeneProduct ensembl:ENSG00000088305
WDHD1 GeneProduct ensembl:ENSG00000198554
JARID2 GeneProduct ensembl:ENSG00000008083
CTBP2 GeneProduct ensembl:ENSG00000175029
MTF2 GeneProduct ensembl:ENSG00000143033
ZIC5 GeneProduct ensembl:ENSG00000139800
AEBP2 GeneProduct ensembl:ENSG00000139154
NCAPG2 GeneProduct ensembl:ENSG00000146918
ZNF281 GeneProduct ensembl:ENSG00000162702
GRHL2 GeneProduct ensembl:ENSG00000083307
TET1 GeneProduct ensembl:ENSG00000138336


  1. T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification. Yamaguchi TP, Takada S, Yoshikawa Y, Wu N, McMahon AP. Genes Dev. 1999 Dec 15;13(24):3185–90. PubMed Europe PMC Scholia
  2. Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm. Bessho Y, Miyoshi G, Sakata R, Kageyama R. Genes Cells. 2001 Feb;6(2):175–85. PubMed Europe PMC Scholia
  3. Dll1 is a downstream target of Tbx6 in the paraxial mesoderm. White PH, Chapman DL. Genesis. 2005 Jul;42(3):193–202. PubMed Europe PMC Scholia
  4. Smad6 inhibits the transcriptional activity of Tbx6 by mediating its degradation. Chen YL, Liu B, Zhou ZN, Hu RY, Fei C, Xie ZH, et al. J Biol Chem. 2009 Aug 28;284(35):23481–90. PubMed Europe PMC Scholia
  5. The Nodal inhibitor Lefty is negatively modulated by the microRNA miR-302 in human embryonic stem cells. Barroso-delJesus A, Lucena-Aguilar G, Sanchez L, Ligero G, Gutierrez-Aranda I, Menendez P. FASEB J. 2011 May;25(5):1497–508. PubMed Europe PMC Scholia
  6. Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells. Takemoto T, Uchikawa M, Yoshida M, Bell DM, Lovell-Badge R, Papaioannou VE, et al. Nature. 2011 Feb 17;470(7334):394–8. PubMed Europe PMC Scholia
  7. miR-125b promotes early germ layer specification through Lin28/let-7d and preferential differentiation of mesoderm in human embryonic stem cells. Wong SSY, Ritner C, Ramachandran S, Aurigui J, Pitt C, Chandra P, et al. PLoS One. 2012;7(4):e36121. PubMed Europe PMC Scholia