Transcriptional and Epigenetic Mechanisms Governing Epidermal Stem Cell Regulation

March 2026 in “ Frontiers in Cell and Developmental Biology ”

Shaelin Lamb, Zuri Omari, Lindsey Seldin

Studysummary This review reports that transcriptional and epigenetic mechanisms in epithelial stem cells guide their fate in the epidermis and hair follicles, crucial for skin homeostasis, but disruptions can lead to disease.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

This review examines the transcriptional and epigenetic mechanisms that regulate epidermal and hair follicle stem cells, crucial for skin maintenance and regeneration. It highlights the roles of transcription factors like p63, YAP, TCF3, SOX9, and LHX2, and epigenetic regulators such as polycomb repressive complexes and histone modifiers in maintaining stem cell identity and function. The review underscores the importance of these mechanisms in balancing stem cell self-renewal and differentiation, with disruptions leading to skin diseases like basal cell carcinoma, psoriasis, and hidradenitis suppurativa. It also discusses the plasticity of hair follicle stem cells in aiding epidermal regeneration and the potential of single-cell technologies to uncover stem cell heterogeneity and chromatin landscapes. Understanding these regulatory networks is vital for developing therapeutic strategies for skin disorders.

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6 citations , July 2023 in “Nature cell biology”

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7 citations , August 2022 in “Experimental dermatology”

This review discusses the role of YAP/TAZ proteins in skin cancer physiology and tumorigenesis, and the potential of targeting these proteins in skin cancer treatments, but presents no new experimental findings.

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22 citations , October 2021 in “Cold Spring Harbor Perspectives in Biology”

This review discusses the interactions and signals affecting skin stem cells and their environments but reports no new experimental results; the authors highlight the need for understanding these processes to enhance tissue rejuvenation and repair.

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26 citations , December 2019 in “Stem Cell Reports”

This study found that transient hypomethylation of histone H3 K4/9/27me3 is crucial for the proper dynamics of adult skin epithelial stem cells and effective tissue repair in mice.

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105 citations , October 2017 in “Stem cells”

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38 citations , April 2017 in “PLOS Genetics”

This study found that human progenitor keratinocytes form unique complements of enhancers and super-enhancers during differentiation and migration, influencing gene expression and skin disease variant enrichment.

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31 citations , April 2016 in “Nature communications”

This study found that in adult mouse skin, reduced levels of histone H3 K4/K9/K27me3 during hair follicle stem cell quiescence are linked to proper tissue homeostasis.

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142 citations , February 2016 in “Science”

This review discusses the role of Foxc1 and type XVII collagen in hair follicle stem cell quiescence and aging, identifying mechanisms that relate to hair thinning and hair loss, and reports no new results.

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321 citations , March 2015 in “Nature”

This study found that super-enhancers are essential for hair follicle stem cell identity, lineage commitment, and plasticity in mice, with SOX9 being a key regulator of these chromatin dynamics.

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84 citations , October 2014 in “PLoS Genetics”

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173 citations , January 2014 in “Nature Cell Biology”

This study found that Wnt signalling activates hair follicle fate in hair follicle stem cells by relieving TCF3/4–TLE-mediated repression, with β-catenin being crucial for this process.

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52 citations , April 2013 in “Developmental Cell”

This study found that Brg1, a chromatin-remodeling enzyme, plays a critical role in hair regeneration and early epidermal repair by regulating bulge stem cells through a Brg1-Shh interaction.

Lef1 Contributes to the Differentiation of Bulge Stem Cells by Nuclear Translocation and Cross-Talk with the Notch Signaling Pathway

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57 citations , January 2013 in “International Journal of Medical Sciences”

This study reports that Lef1 plays a crucial role in promoting bulge stem cell differentiation towards hair fate by activating β-catenin and downstream signaling pathways during hair follicle development.

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23 citations , June 2012 in “PLOS ONE”

This study found that KLF4 expression in mouse hair follicle stem cells is important for effective cutaneous wound healing, with its knockdown leading to reduced stem cell populations and delayed healing.

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43 citations , January 2012 in “Biological Research”

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166 citations , September 2011 in “The Journal of Cell Biology”

This study found that the p63 transcription factor plays a role in epidermal morphogenesis by regulating Satb1 expression, impacting chromatin architecture and gene expression in epidermal progenitor cells.

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396 citations , May 2011 in “Cell stem cell”

This study found that Shh from neurons signals to Gli1-expressing cells in the hair follicle, cultivating a niche where these bulge cells can potentially transform into epidermal stem cells in wound healing.

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178 citations , April 2011 in “Journal of Clinical Investigation”

This study found that the phenotype of Hedgehog/Gli-driven skin tumors in mice depends on the cell of origin, tissue context, and level of oncogenic signaling.

research EZH1 and EZH2 Co-Govern Histone H3K27 Trimethylation and Are Essential for Hair Follicle Homeostasis and Wound Repair

354 citations , February 2011 in “Genes & Development”

This study found that abolishing H3K27me3 in mouse skin by targeting Ezh2 and Ezh1 affects hair follicle development and epidermal behavior, revealing functional differences between these tissues.

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351 citations , February 2010 in “Nature Cell Biology”

Basal cell carcinoma mostly starts from cells in the upper skin layers, not hair follicle stem cells.

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759 citations , February 2009 in “Current Biology”

This review summarizes fundamental concepts and recent advancements in hair follicle biology, including insights from mouse models into broader molecular and cellular processes relevant to regeneration and development.

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415 citations , January 2008 in “Cell”

NFATc1 controls hair stem cell activity, affecting hair growth and could be a target for hair loss treatments.

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1279 citations , November 2005 in “Nature Medicine”

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479 citations , January 2005 in “BioEssays”

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92 citations , May 2004 in “Journal of Investigative Dermatology”

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182 citations , May 2003 in “Development”

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