ArticleeLife2017
A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 69 citations in OpenAlex.
- Article
- Cell volume regulates terminal differentiation of cultured human epidermal keratinocytes.Journal of cell science · 2025Article
- Dual-Specificity Protein Phosphatases Targeting Extracellular Signal-Regulated Kinases: Friends or Foes in the Biology of Cancer?International journal of molecular sciences · 2025Review
- Optimal performance objectives in the highly conserved bone morphogenetic protein signaling pathway.NPJ systems biology and applications · 2024Article
- Neutral evolution of snoRNA Host Gene long non-coding RNA affects cell fate control.The EMBO journal · 2024Article
- Single-cell RNA sequencing of human epidermis identifies Lunatic fringe as a novel regulator of the stem cell compartment.Stem cell reports · 2023Article
- SPRY4-dependent ERK negative feedback demarcates functional adult stem cells in the male mouse germline†.Biology of reproduction · 2023Article
- Article
- SALL4 correlates with proliferation, metastasis, and poor prognosis in prostate cancer by affecting MAPK pathway.Cancer medicine · 2023Article
- Aging and obesity prime the methylome and transcriptome of adipose stem cells for disease and dysfunction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- ERK1/2 signalling dynamics promote neural differentiation by regulating chromatin accessibility and the polycomb repressive complex.PLoS biology · 2022Article
- Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction.Nature communications · 2022Article
- A reductionist approach to determine the effect of cell-cell contact on human epidermal stem cell differentiation.Acta biomaterialia · 2022Article
- Understanding Human Epidermal Stem Cells at Single-Cell Resolution.The Journal of investigative dermatology · 2022Review
- CDK9 activity switch associated with AFF1 and HEXIM1 controls differentiation initiation from epidermal progenitors.Nature communications · 2022Article
- A phosphatase-centric mechanism drives stress signaling response.EMBO reports · 2021Article
- Minor Allele Frequencies and Molecular Pathways Differences for SNPs Associated with Amyotrophic Lateral Sclerosis in Subjects Participating in the UKBB and 1000 Genomes Project.Journal of clinical medicine · 2021Article
- Therapeutic wavelengths of ultraviolet B radiation activate apoptotic, circadian rhythm, redox signalling and key canonical pathways in psoriatic epidermis.Redox biology · 2021Article
- Developmental cell programs are co-opted in inflammatory skin disease.Science (New York, N.Y.) · 2021Article
- Computational Stem Cell Biology: Open Questions and Guiding Principles.Cell stem cell · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.