A collaboration between the Lamond and Watt groups identifies a key role of specific protein phosphatases in human skin stem cell commitment to differentiation.  

A collaborative study, carried out by the Lamond group and the Watt laboratory at King’s College London, entitled “A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis”, has been accepted for publication in eLife (Mishra et al., eLife 2017). Described by the editor as a ‘tour de force’ analysis of phosphatase function in human skin stem cells during differentiation, this study integrates transcriptomic and proteomic data to identify the role of protein phosphatases in regulation of epidermal differentiation. This identifies five protein phosphatases, i.e., DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA, which promote differentiation by negatively regulating ERK & MAPK and positively regulating AP1 transcription factors. Conversely, DUSP10 expression was shown to antagonise commitment. These protein phosphatases form an auto-regulatory dynamic network, including transient positive and negative interactions, that maintains epidermal homeostasis by controlling the onset and duration of commitment to differentiation.

Read eLife publication here.

Image: Figure 2b: Effect of knocking down the 22 phosphatases identified in (a) on clonal growth of keratinocytes. Values plotted are average % clonal growth in n = 3 independent screens with n = 3 independent cultures per screen. Green: siSCR control. Red, blue: phosphatases with statistically significant effects on colony formation are shown (red: increase; blue: decrease). Grey: no statistically significant effect.