Among them, we found the principal components of major regulatory clusters, involving inflammatory responses (IFNy, IL6, several members of the interleukin 1 pathway, including ILIA, IL1B, IL1RN, and the TNF pathway members TNF, TNFAIP6, TNFSF15, TNFRSF9), angiogenesis (CXCL10, PTGS2), immune regulation (CD80, CD274, CSF3, IL23R), leukocyte chemotaxis (CCL2, CCL3, CCL4, CCL20, CCL23, CCL3L3, CXCL1, CXCL2, CXCL5, CXCL9), transcriptional regulation (EGR1, GATA6, HEY1
), proliferation (CDKN2B, FGFR1), adhesion (ITGB8), extracellular matrix remodeling (ADAMTS4), cell-cell communication (GJB2), cell signaling (EDNRB, IRS1, RIN2), ion transmembrane transport (KCNJ2, CLIC4), and response to oxidative stress (SOD2).
Critical myogenic genes involved in myotube differentiation including Pax7, myogenin (MyoG), myosin heavy chain 1 (MYH1), hairy/enhancer-of-split related with YRPW motif protein 1 (Hey1
), DNA-binding protein inhibitor ID1 (ID1), and activin A receptor type I (ACVR1) were precipitously downregulated in MyoD KO QM7#4 cells (Table 2).
AT reduces the expression of Hedgehog pathway target genes, such as PTCH1, N-Myc, and GLI2, but also the expression of the Notch pathway target genes HES1, HES5, and HEY1
and that of the pluripotency factor SOX2 .
The second class contains genes that control cell differentiation during the development of a number of tissues (SOX11, SOX18, HEY1
, CART1, PRX2, SMAD7, ID1).