ArticlePLoS computational biology2015
Dissecting the calcium-induced differentiation of human primary keratinocytes stem cells by integrative and structural network analyses.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- History-dependent switch-like differentiation of keratinocytes in response to skin barrier damage.PLoS computational biology · 2025Article
- The Rho GTPase exchange factor Vav2 promotes extensive age-dependent rewiring of the hair follicle stem cell transcriptome.Frontiers in cell and developmental biology · 2023Article
- Conserved exchange of paralog proteins during neuronal differentiation.Life science alliance · 2022Article
- Article
- Characterization of Human Keratinocyte Cell Lines for Barrier Studies.JID innovations : skin science from molecules to population health · 2021Article
- Predicted 'wiring landscape' of Ras-effector interactions in 29 human tissues.NPJ systems biology and applications · 2021Article
- Epidermal Lamellar Body Biogenesis: Insight Into the Roles of Golgi and Lysosomes.Frontiers in cell and developmental biology · 2021Review
- In Silico Analysis of the Age-Dependent Evolution of the Transcriptome of Mouse Skin Stem Cells.Cells · 2020Article
- Investigating the effect of dependence between conditions with Bayesian Linear Mixed Models for motif activity analysis.PloS one · 2020Article
- Calmodulin (CaM) Activates PI3Kα by Targeting the "Soft" CaM-Binding Motifs in Both the nSH2 and cSH2 Domains of p85α.The journal of physical chemistry. B · 2018Article
- Systems level expression correlation of Ras GTPase regulators.Cell communication and signaling : CCS · 2018Article
- Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome.Genome biology · 2018Article
- Prolonging culture of primary human keratinocytes isolated from suction blisters with the Rho kinase inhibitor Y-27632.PloS one · 2018Article
- Phosphorylated Calmodulin Promotes PI3K Activation by Binding to the SHBiophysical journal · 2017Article
- CDH1 regulates E2F1 degradation in response to differentiation signals in keratinocytes.Oncotarget · 2017Article
- Single-Cell Transcriptomics Reveals that Differentiation and Spatial Signatures Shape Epidermal and Hair Follicle Heterogeneity.Cell systems · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The molecular details underlying the time-dependent assembly of protein complexes in cellular networks, such as those that occur during differentiation, are largely unexplored. Focusing on the calcium-induced differentiation of primary human keratinocytes as a model system for a major cellular reorganization process, we look at the expression of genes whose products are involved in manually-annotated protein complexes. Clustering analyses revealed only moderate co-expression of functionally related proteins during differentiation. However, when we looked at protein complexes, we found that the majority (55%) are composed of non-dynamic and dynamic gene products ('di-chromatic'), 19% are non-dynamic, and 26% only dynamic. Considering three-dimensional protein structures to predict steric interactions, we found that proteins encoded by dynamic genes frequently interact with a common non-dynamic protein in a mutually exclusive fashion. This suggests that during differentiation, complex assemblies may also change through variation in the abundance of proteins that compete for binding to common proteins as found in some cases for paralogous proteins. Considering the example of the TNF-α/NFκB signaling complex, we suggest that the same core complex can guide signals into diverse context-specific outputs by addition of time specific expressed subunits, while keeping other cellular functions constant. Thus, our analysis provides evidence that complex assembly with stable core components and competition could contribute to cell differentiation.
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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.