Disruption of Smad4 in Mouse Epidermis Leads to Depletion of Follicle Stem Cells

December 2008 in “ Molecular biology of the cell ”

Leilei Yang, Lijuan Wang, Xiao Yang

Studysummary This study found that disrupting Smad4 signaling in young mice led to overactivation of follicle stem cells, causing hyperplasia and depletion of the stem cell niche. Our plain-language summary of this paper — not a Tressless recommendation.

In a study from 2009, researchers found that disrupting Smad4, a key component of TGF-beta signaling, in the epidermis of young mice led to the overactivation of follicle stem cells (SCs) in the hair follicle bulge. This overactivation caused an increase in the proliferation of these cells, resulting in hyperplasia of the interfollicular epidermis, hair follicles, and sebaceous glands. However, this increased activity eventually depleted the stem cell niche, as evidenced by the loss of bromodeoxyuridine (BrdU) label-retaining cells, and a decrease in keratin 15 (K15) and CD34 expression. Additionally, the colony-forming efficiency of keratinocytes from the Smad4 mutant mice was significantly reduced. The depletion of follicle SCs was associated with increased nuclear localization of beta-catenin and higher expression of c-Myc. The study concluded that Smad4 is crucial for the maintenance of follicle stem cells.

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research The Up-Regulation of 14-3-3 Proteins in Smad4 Deficient Epidermis and Hair Follicles at Catagen

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This study found that CD34 is necessary for TPA-induced activation of hair follicle stem cells and tumor formation in mice, with CD34 knockout mice showing delayed and reduced tumor development compared to wild-types.

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This review explores how adult skin epithelia preserve stem cell populations for hair follicle regeneration and wound healing, but reports no new experimental results.

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research Defining the Impact of Beta-Catenin/Tcf Transactivation on Epithelial Stem Cells

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This study found that stabilized beta-catenin is crucial for activating stem cell transition from quiescence to proliferation in hair follicles by influencing gene expression within the stem cell niche.

research Transient Activation of Beta-Catenin Signaling in Adult Mouse Epidermis Induces New Hair Follicles, Continuous Activation Maintains Tumors

335 citations , March 2004 in “Development”

This study found that continuous β-catenin signaling in adult mouse epidermis can reprogram hair follicles to form benign tumors, which regress after the signaling is discontinued.

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This study found that Myc activation in mouse epidermis impairs keratinocyte adhesion and motility by downregulating extracellular matrix and cytoskeleton proteins, affecting hair lineage differentiation.

research Tcf3 and Lef1 Regulate Lineage Differentiation of Multipotent Stem Cells in Skin

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research Deregulated Expression of c-Myc Depletes Epidermal Stem Cells

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research C-Myc Activation in Transgenic Mouse Epidermis Results in Mobilization of Stem Cells and Differentiation of Their Progeny

338 citations , April 2001 in “Current Biology”

This study found that transient activation of c-Myc in transgenic mice stimulates keratinocyte proliferation and sebocyte differentiation, affecting normal epidermal and hair follicle development.

research Inhibition of BMP Signaling Affects Growth and Differentiation in the Anagen Hair Follicle

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research Multiple Roles for Activated LEF/TCF Transcription Complexes During Hair Follicle Development and Differentiation

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This study found that LEF1/TCF3 is necessary but not sufficient for TOPGAL activation in hair follicle development, indicating complex regulation in the skin.