FIGURE 3.

Cooperation of squamous, stress and epigenetic regulators in driving skin epithelial stem cell plasticity. (A) TFs such as p63 are regulated at multiple levels, including post-translational modifications by phosphorylation and ubiquitination, post-transcriptional regulation by miRNAs, alternative splicing and positive feedback regulations. (B) A group of TFs govern hair follicle stem cell (HFSC) quiescence, including SOX9, LHX2, TCF3, TCF4, NFATC1 and FOXC1, while KLF5 is specifically enriched in EpdSCs. Upon wounding, HFSCs induce the expression of KLF5, which is coexpressed with SOX9, ETS2, AP-1 and p63, among others, resulting in stem cell lineage infidelity, an epigenetically rewired state that is functionally required for wound repair. (C) Several groups of epigenetic factors are integrated in the regulation of EpdSC proliferation (P) and differentiation (D), including histone deacetylases (HDAC1/2, HDAC3), histone methyltransferases, demethylases, and their regulators (EZH2, CBX4, KMT2C/D, KMT4A, KMT6B), chromatin remodelers (BRG1, SATB1, ACTL6A), and DNA methyltransferases and regulators (DNMT1, DNMT3A/B, UHRF1). KMT2C is also known as MLL3, KMT2D as MLL2, KDM4A as JMJD2, and KDM6B as JMJD3. The hypothetical epigenetic factor is depicted arbitrarily with multiple activities