Diverse Mechanisms for Endogenous Regeneration and Repair in Mammalian Organs

May 2018 in “ Nature ”

J. Michael Wells, Fiona M. Watt

endogenous regeneration stem cells cell plasticity immune interactions resident stem cells progenitor cell proliferation hair follicles Lgr5-positive stem cells Wnt-responsive hepatocytes lineage tracing transcription factors

Studysummary Mammalian organs regenerate using stem cells and cell plasticity, but this ability declines with age.

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The document discussed the diverse mechanisms of endogenous regeneration and repair in mammalian organs, focusing on the role of stem cells, cell plasticity, and immune interactions. It highlighted how regenerative organs like the skin use resident stem cells, while organs with less turnover, such as the liver, rely on progenitor cell proliferation. The study noted that injury can reveal cell plasticity, which diminishes with age, and explored therapeutic approaches to harness this plasticity for tissue repair, with caution regarding cancer risks. Specific examples included hair follicles in skin healing, Lgr5-positive stem cells in gastric renewal, and Wnt-responsive hepatocytes in liver maintenance. The document also addressed the decline in regenerative capacity with age, the potential for rejuvenating aged organs, and the importance of lineage tracing and transcription factors in research.

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research Type XVII Collagen Coordinates Proliferation in the Interfollicular Epidermis

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This study found that COL17 deficiency in neonatal mice causes abnormal skin cell proliferation due to disrupted Wnt signaling, while replenishing or overexpressing COL17 can reverse this effect in both neonatal and aged skin.

research Dermal Blimp1 Acts Downstream of Epidermal TGFβ and Wnt/β-Catenin to Regulate Hair Follicle Formation and Growth

85 citations , June 2017 in “Journal of Investigative Dermatology”

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research Wounding Induces Dedifferentiation of Epidermal Gata6+ Cells and Acquisition of Stem Cell Properties

143 citations , May 2017 in “Nature cell biology”

This study found that the transcription factor Gata6 regulates the sebaceous duct lineage identity and plays a crucial role in epidermal wound healing by enabling dedifferentiation and broader lineage capabilities in post-mitotic cells.

research Epithelial-Mesenchymal Micro-Niches Govern Stem Cell Lineage Choices

214 citations , April 2017 in “Cell”

This study found that micro-niches within hair follicles create heterogeneity among stem cells and transit-amplifying cells, leading to specialized progenitors that control tissue morphogenesis and regeneration.

research Regeneration of Fat Cells from Myofibroblasts During Wound Healing

408 citations , January 2017 in “Science”

This study found that hair follicles in mice and humans can convert wound-related myofibroblasts into adipocytes, suggesting a potential pathway to reduce scar formation by activating BMP signaling.

Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition

research Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition

174 citations , November 2016 in “Cell stem cell”

This study found that squamous cell carcinomas from hair follicle stem cells are more prone to epithelial to mesenchymal transition and metastasis than those from interfollicular epidermis, due to distinct chromatin landscapes.

research Epigenetic Control of Adult Stem Cell Function

179 citations , July 2016 in “Nature Reviews Molecular Cell Biology”

This review examines how epigenetic dysregulation affects adult stem cell function, noting that impacts range from minor to serious disruptions in tissue homeostasis and potential cancer development.

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 Epidermal β-Catenin Activation Remodels the Dermis via Paracrine Signaling to Distinct Fibroblast Lineages

115 citations , February 2016 in “Nature Communications”

The authors concluded that the dermal response to epidermal Wnt/β-catenin signaling depends on distinct fibroblast lineages, with each responding to different paracrine signals such as Hedgehog and TGF-β.

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research Compartmentalized Epidermal Activation of β-Catenin Differentially Affects Lineage Reprogramming and Underlies Tumor Heterogeneity

54 citations , January 2016 in “Cell reports”

This study found that different epidermal stem cell populations contribute to the formation of various skin tumors and new hair follicles following β-catenin activation in the adult epidermis.

research Inhibition of β-Catenin Signaling in Dermal Fibroblasts Enhances Hair Follicle Regeneration During Wound Healing

87 citations , January 2016 in “Development”

This study suggests that the postnatal loss of hair follicle formation in wounds may be due to elevated Wnt/β-catenin activation in the dermis, affecting fibroblast function in mice.

Modulating the Stem Cell Niche for Tissue Regeneration