Abstract:
At present, a technical platform for inducing goat(Capra hircus) ear margin fibroblasts control group to transdifferentiate into mammary epithelial cells(named CiMECs or 5i8d, the latter will be subject to 5i8d to indicate the treatment conditions) has been established by small molecular compounds. In this study, the trimethylation of lysine 4 on histone H3 protein subunit(H3K4me3)and the trimethylation of lysine 27 on histone H3 protein subunit(H3K27me3) of chromatin immunoprecipitation(ChIP) were sequenced in cells before and after transdifferentiation(Control and 5i8d) to explore the changes of H3K4me3 and H3K27me3 expression patterns in cells before and after transdifferentiation. The differential Peaks-related genes of H3K4me3 were enriched in the pathways associated with mammary gland development and differentiation GO items, including epithelial morphogenesis, regulation of MAPK(Mitogen activated protein kinase) cascade, Wnt(Wingless type MMTV integration site family) receptor pathway and β-catenin receptor pathway which indicated that the fate of mammary epithelial cells had been activated, the differential Peaks-related genes of H3K27me3 were enriched in Go items such as lamina propria, plasma propria and actin filaments, suggesting that the pathways maintained fibroblast membrane and its skeletal properties were inhibited, furthermore fibroblast lineage was broken. The differential Peaks-related genes of H3K4me3 were enriched in these KEGG pathway, such as MAPK signaling pathway, insulin and secretion signaling pathway, PI3K-Akt(Phosphatidylinositol 3-kinase protein kinase B) signaling pathway and estrogen signaling pathway. Moreover, these signaling pathways were closely related to mammary gland development and differentiation, showing that the lineage of mammary gland epithelial cells was triggered. The differential Peaks-related genes of H3K27me3 were mainly enriched in KEGG signaling pathways-adhesion plaque signaling pathway, ECM receptor interaction signaling pathway and cell adhesion factor, manifesting that the pathways related to the connectivity between fibroblasts were inhibited. Above all, it was inferred that the cell lineage of goat ear margin fibroblasts transformed from fibroblasts to mammary gland epithelial cells with lactation after eight days of this successful induction. The study provides some theoretical support for the study of fate determination, developmental differentiation and lactation.