Table 1. Distribution of genes participating in six signaling pathways in the ES clusters.
Pathway | Components | Mouse specific: Clusters (2, *), (3, *) but not (2, 3), (3, 3) | Human specific: Clusters (*, 3), but not (2, 3), (3, 3) | Shared: Clusters (2, 3), (3, 3) | Comment |
JAK-STAT | Extracellular & membrane | LIF, IL2R, IL4R, IL6R | mES specific | ||
Downstream factors | JAK3, TK2#, PTPRC, PTPRF, PTPRN, SOSC3, PINK1* | ||||
Transcription regulators | STAT3#, STAT4, STAT5A, STAT5B, STAT6 | ||||
NOTCH | Extracellular & membrane | NOTCH4, JAGGED2, MFNG | |||
Downstream factors | |||||
Transcription regulatorsF | NCOA1* | ||||
TGFβ | Extracellular & membrane | TGFβ1, TGFβR1 | BMP4, ACVR2B | LEFTY, BMPR1 | Alternatively implemented |
Downstream factors | MAPK3, PINK1* | PPP1CC*, SAR1A | |||
Transcription regulators | [SMAD7]&, SKIL&, NCOA1* | [SMAD2]& (interact with TGIF1) | TGIF1& | ||
WNT | Extracellular & membrane | [FRIZZLED9], H{LRP5} | [FRIZZLED3], {LRP6} | [FRIZZLED7] | |
Downstream factors | RHOA | CSNK2A1, CSNK1D | CSNK2B | ||
Transcription regulators | [TLE4]&, LEF1, MYC | [TLE1]&, TCF7L2 | CTBP2& | ||
MAPK | Extracellular & membrane | FGF4, MET*, EGFR, GRB2 | FGFR2 | {FGF2}, TDGF1 | |
Downstream factors | [ARAF], {PTPRC}, {PTPRF}, {PTPRN}, [MAP3K6], [MAP2K7], [MAPK3] | [KRAS], {PTPRK}, {PRPRG}, {PTPN11}, [MAP3K7] | [RAF1] | ||
Transcription regulators | ATF4 | ||||
VEGF | Extracellular & membrane | Unlikely to be expressed in ES cells | |||
Downstream factors | PINK1*, PLCD1, PLA2 | PTK2, PPP1CC*, CLK2 | |||
Transcription regulators |
Genes in the same family are embraced with the same parenthesis. Genes with a * are involved in the multiple pathways. Genes with & signs are transcriptional repressors or co-repressors. Genes with a # have abundant transcripts in mES cells, but they do not show obvious up or down regulation during differentiation of mES cells.