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| Status |
Public on Oct 17, 2017 |
| Title |
A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Epidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation. The transition between the two cell states, termed commitment, is poorly understood. Here we characterise commitment by integrating transcriptomic and proteomic data from disaggregated primary human keratinocytes held in suspension to induce differentiation. Cell detachment induces several protein phosphatases, five of which - DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA – promote differentiation by negatively regulating ERK MAPK and positively regulating AP1 transcription factors. Conversely, DUSP10 expression antagonises commitment. The phosphatases form a dynamic network of transient positive and negative interactions that change over time, with DUSP6 predominating at commitment. Boolean network modelling identifies a mandatory switch between two stable states (stem and differentiated) via an unstable (committed) state. Phosphatase expression is also spatially regulated in vivo and in vitro. We conclude that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment.
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| Overall design |
Total RNA obtained from keratinocytes which were subjected to suspension induced differentiation (time course experiment).
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| Contributor(s) |
Mishra A, Pisco AO, Watt FM |
| Citation(s) |
29043977 |
| |
| Submission date |
Sep 17, 2015 |
| Last update date |
Sep 12, 2019 |
| Contact name |
ajay Mishra |
| E-mail(s) |
ajay.mishra@kcl.ac.uk
|
| Organization name |
King's College London
|
| Department |
Centre for Stem Cells and Regenerative Medicine
|
| Street address |
Great Maze Pond
|
| City |
London |
| ZIP/Postal code |
SE1 9RT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL10904 |
Illumina HumanHT-12 V4.0 expression beadchip (gene symbol) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA296097 |
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