Dab2, an Adaptor Protein, Regulates Self-Renewal of Hair Follicle Stem Cells

May 2024 in “ Communications Biology ”

Sayoni Roy, Darshan Mehta, Akshay Paradkar, Gopal Chovatiya, Sanjeev K. Waghmare

Disabled 2 Dab2 hair follicle stem cells HFSC Nfatc1 Col17a1 decorin Sirt2 Sirt7

Studysummary This study found that Dab2 conditional knockout mice experienced delayed hair follicle cycles and reduced hair follicle stem cell activity, suggesting Dab2's crucial role in regulating stem cell activation and anti-aging process in hair follicles. Our plain-language summary of this paper — not a Tressless recommendation.

The study investigates the role of the adaptor protein Disabled 2 (Dab2) in hair follicle stem cells (HFSCs) using Dab2 conditional knockout (Dab2-cKO) mice. Findings reveal that Dab2-cKO mice experience a delay in the hair follicle cycle due to disrupted HFSC activation, a reduction in HFSC numbers, and diminished colony-forming ability. These mice also exhibit extended HFSC quiescence with increased Nfatc1 expression and decreased expression of anti-aging genes like Col17a1, decorin, Sirt2, and Sirt7. Additionally, aged Dab2-cKO mice fail to fully recover their hair coat, indicating accelerated aging. This study is the first to demonstrate Dab2's critical role in regulating HFSC activation and self-renewal.

View this study on nature.com →

Discuss this study in the Community →

Research cited in this study

18 / 18 results

research SIRT7 Activates Quiescent Hair Follicle Stem Cells to Ensure Hair Growth in Mice

38 citations , July 2020 in “EMBO journal”

In this study, researchers found that SIRT7 activates quiescent hair follicle stem cells to promote hair growth in mice by triggering the telogen-to-anagen cycle transition, with potential implications for age-related hair loss.

research Context-Dependent Effect of sPLA2-IIA Induced Proliferation on Murine Hair Follicle Stem Cells and Human Epithelial Cancer

13 citations , September 2019 in “EBioMedicine”

This study found that Secretory Phospholipase A2-IIA (sPLA2-IIA) promotes proliferation through JNK/c-Jun signaling, distinctively affecting normal stem cells and cancer cells, suggesting it as a potential target for cancer treatment.

research Extracellular Proteoglycan Decorin Maintains Human Hair Follicle Stem Cells

11 citations , October 2018 in “The Journal of Dermatology”

This study suggests that decorin may help maintain hair follicle stem cells and its reduced expression could contribute to age-related hair loss.

Baicalin Increases Hair Follicle Development by Enhancing Canonical Wnt/β-Catenin Signaling and Activating Dermal Papilla Cells in Mice

research Baicalin Increases Hair Follicle Development by Enhancing Canonical Wnt/β-Catenin Signaling and Activating Dermal Papilla Cells in Mice

23 citations , January 2018 in “International Journal of Molecular Medicine”

This study reported that baicalin activates the Wnt/β-catenin signaling pathway in mouse hair follicles, suggesting its potential as a topical treatment for hair loss.

research sPLA2-IIA Overexpression in Mice Epidermis Depletes Hair Follicle Stem Cells and Induces Differentiation Mediated Through Enhanced JNK/c-Jun Activation

9 citations , June 2016 in “Stem cells”

In this study, overexpression of secretory phospholipase A2 Group-IIA in transgenic mice led to depletion of hair follicle stem cells and increased differentiation, linked to changes in histone modifications.

research Hair Follicle Aging Is Driven by Transepidermal Elimination of Stem Cells via COL17A1 Proteolysis

242 citations , February 2016 in “Science”

This research found that Foxc1 transcription factor and COL17A1 are critical in regulating quiescence and hair thinning in hair follicle stem cells, with aging-related DNA damage leading to hair loss.

research Regenerative Hair Waves in Aging Mice and Extra-Follicular Modulators Follistatin, Dkk1, and Sfrp4

75 citations , March 2014 in “Journal of Investigative Dermatology”

This study found that aging mice experience slower and more fragmented hair cycle waves, but transplanting aged skin to a young host can partially restore hair cycling, implicating extracellular factors.

research Spatial Organization Within a Niche as a Determinant of Stem-Cell Fate

394 citations , October 2013 in “Nature”

research Competitive Balance of Intrabulge BMP/Wnt Signaling Reveals a Robust Gene Network Ruling Stem Cell Homeostasis and Cyclic Activation

176 citations , January 2013 in “Proceedings of the National Academy of Sciences”

This study reveals an antagonistic competition between BMP and Wnt signaling within stem cells, influencing their fate towards hair germ characteristics based on the BMP/Wnt activity ratio.

research Coordinated Activation of Wnt in Epithelial and Melanocyte Stem Cells Initiates Pigmented Hair Regeneration

260 citations , June 2011 in “Cell”

This study found that Wnt signaling in the hair follicle is crucial for coordinating the behavior of epithelial and melanocyte stem cells, which drives hair regeneration and melanocyte differentiation in mice.

research Hair Follicle Stem Cells Provide a Functional Niche for Melanocyte Stem Cells

283 citations , February 2011 in “Cell stem cell”

COL17A1 is crucial for preventing hair graying and loss by supporting hair and pigment stem cells.

Bald Scalp in Men with Androgenetic Alopecia Retains Hair Follicle Stem Cells but Lacks CD200-Rich and CD34-Positive Hair Follicle Progenitor Cells

research Bald Scalp in Men with Androgenetic Alopecia Retains Hair Follicle Stem Cells but Lacks CD200-Rich and CD34-Positive Hair Follicle Progenitor Cells

235 citations , January 2011 in “Journal of Clinical Investigation”

This study found that androgenetic alopecia may involve a defect in the conversion of hair follicle stem cells to progenitor cells, as demonstrated by a reduced presence of progenitor cells in bald scalp samples.

research The Hair Follicle as a Dynamic Mini-Organ

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.

research Nfatc1 Balances Quiescence and Proliferation of Skin Stem Cells

415 citations , January 2008 in “Cell”

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

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

384 citations , June 2005 in “Genes & development”

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 Expression of ΔNLef1 in Mouse Epidermis Results in Differentiation of Hair Follicles into Squamous Epidermal Cysts and Formation of Skin Tumors

297 citations , January 2002 in “Development”

In this study, repressing β-catenin/Lef1 signalling in mouse epidermis led to progressive hair loss, dermal cysts, and spontaneous skin tumors with sebaceous differentiation, indicating altered keratinocyte differentiation and potential tumourigenic processes.

Expression of Calcium-Binding S100 Proteins A4 and A6 in Regions of the Epithelial Sac Associated with the Onset of Hair Follicle Regeneration

research Expression of Calcium-Binding S100 Proteins A4 and A6 in Regions of the Epithelial Sac Associated with the Onset of Hair Follicle Regeneration

72 citations , June 2001 in “Journal of Investigative Dermatology”

This study suggests that S100A4 and S100A6 proteins may play key roles in activating stem cells for hair follicle regeneration in mice.

research WNT Signaling in the Control of Hair Growth and Structure

271 citations , March 1999 in “Developmental biology”

This study reveals that overexpression of Wnt3 in transgenic mouse skin leads to a short-hair phenotype and cyclical balding due to structural defects in hair shafts, highlighting a role for WNT signaling in hair growth regulation.