<i>Axin2</i>
            marks quiescent hair follicle bulge stem cells that are maintained by autocrine Wnt/β-catenin signaling

Lim, Xinhong; Tan, Si Hui; Yu, Ka Lou; Lim, Sophia Beng Hui; Nusse, Roeland

doi:10.1073/pnas.1601599113

Cited by 100 publications

(96 citation statements)

References 43 publications

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“…We examined the effects of systemic WNT-974 exposure on two other tissues that are reliant upon Wnt signaling for regeneration: hair follicles and cartilage (13,14). In both tissue types, suppression of Wnt signaling, following either depilation or the introduction of puncture wounds in the ear, resulted in delayed hair and cartilage regrowth ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We exploited the responsiveness of homeostatic heart tissue to WNT-974 exposure to identify Wnt-regulated cellular processes that may suppress CM cell cycle reentry. Tissues exposed to WNT-974 exhibit a significant change in expression of genes that contribute to remodeling of the extracellular matrix (ECM), including several that are associated with Wnt/β-catenin signaling (14,(19)(20)(21) (Fig. 2A and Dataset S1).…”

Section: Resultsmentioning

confidence: 99%

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Blockade to pathological remodeling of infarcted heart tissue using a porcupine antagonist

Moon

Zhou

Zhang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The secreted Wnt signaling molecules are essential to the coordination of cell-fate decision making in multicellular organisms. In adult animals, the secreted Wnt proteins are critical for tissue regeneration and frequently contribute to cancer. Small molecules that disable the Wnt acyltransferase Porcupine (Porcn) are candidate anticancer agents in clinical testing. Here we have systematically assessed the effects of the Porcn inhibitor (WNT-974) on the regeneration of several tissue types to identify potentially unwanted chemical effects that could limit the therapeutic utility of such agents. An unanticipated observation from these studies is proregenerative responses in heart muscle induced by systemic chemical suppression of Wnt signaling. Using in vitro cultures of several cell types found in the heart, we delineate the Wnt signaling apparatus supporting an antiregenerative transcriptional program that includes a subunit of the nonfibrillar collagen VI. Similar to observations seen in animals exposed to WNT-974, deletion of the collagen VI subunit, COL6A1, has been shown to decrease aberrant remodeling and fibrosis in infarcted heart tissue. We demonstrate that WNT-974 can improve the recovery of heart function after left anterior descending coronary artery ligation by mitigating adverse remodeling of infarcted tissue. Injured heart tissue exposed to WNT-974 exhibits decreased scarring and reduced Col6 production. Our findings support the development of Porcn inhibitors as antifibrotic agents that could be exploited to promote heart repair following injury.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Blockade to pathological remodeling of infarcted heart tissue using a porcupine antagonist

Moon

Zhou

Zhang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Binding of Wnt ligands to the frizzled receptor results in the nuclear translocation of the transcription factor β‐catenin. Morphogenesis and spacing of PSUs requires canonical Wnt signalling, and continued renewal of both the HF and interfollicular epidermis is also Wnt signalling‐dependent . Loss of functional β‐catenin/Lef1 in mouse epidermis results in SG enlargement and formation of sebaceous tumours (Table ) .…”

Section: Factors Controlling Sebaceous Gland Homeostasismentioning

confidence: 99%

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

et al. 2019

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Summary Background Sebaceous glands (SGs) are appendages of mammalian skin that produce a mixture of lipids known as sebum. Acne vulgaris is an exceptionally common skin condition, characterized by elevated sebum production, altered sebum composition, and the formation of infundibular cysts, called comedones. Comedo‐associated SGs are atrophic, suggesting that comedo formation involves abnormal differentiation of progenitor cells that generate the SG and infundibulum: the ‘comedo switch’. Understanding the biological processes that govern SG homeostasis promises to highlight potential aetiological mechanisms underlying acne and other SG‐associated skin disorders. Results In this review, we discuss the clinical data, genetic mouse models and in vitro research that have highlighted major hormones, paracrine factors, transcription factors and signalling pathways that control SG homeostasis. These include, but are not limited to androgens, progestogens and oestrogens; retinoids; receptor tyrosine kinases such as ErbB family receptors, fibroblast growth factor receptor 2 and insulin/insulin‐like growth factor 1 receptors; peroxisome proliferator‐activated receptor γ; aryl hydrocarbon receptor; and the Wnt signalling pathway. Where possible, the cellular and molecular mechanisms by which these regulatory factors control SG biology are indicated, along with considerations as to how they might contribute to acne pathogenesis. Conclusions Future research should seek to establish the relative importance, and causative relationships, of altered sebum production, sebum composition, inflammation and abnormal differentiation of sebaceous progenitors to the process of comedo formation in acne. Such an understanding will allow for therapeutic targeting of regulatory factors that control SG homeostasis, with the aim of treating acne.

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“…In agreement, Wnt/β‐catenin signaling reporters, TOPGAL or Axin2‐LacZ, are inactive in the telogen HFSCs consistent with the absence of nuclear β‐catenin . A recent study reports that some Wnt ligands are expressed by HFSCs and that Axin2 , a Wnt/β‐catenin signaling target gene, is detectable in the outer bulge compartment throughout telogen, implicating the presence of Wnt/β‐catenin signaling in telogen HFSCs . However, it is unclear whether this low level of Wnt/β‐catenin activity in quiescent HFSCs is required or functional for HFSC maintenance.…”

Section: Wnt Signaling In Skin Epidermal Stem Cellsmentioning

confidence: 99%

Concise Review: Wnt Signaling Pathways in Skin Development and Epidermal Stem Cells

2017

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Mammalian skin and its appendages constitute the integumentary system forming a barrier between the organism and its environment. During development, skin epidermal cells divide rapidly and stratify into a multilayered epithelium, as well as invaginate downward in the underlying mesenchyme to form hair follicles (HFs). In postnatal skin, the interfollicular epidermal (IFE) cells continuously proliferate and differentiate while HFs undergo cycles of regeneration. Epidermal regeneration is fueled by epidermal stem cells (SCs) located in the basal layer of the IFE and the outer layer of the bulge in the HF. Epidermal development and SC behavior are mainly regulated by various extrinsic cues, among which Wnt-dependent signaling pathways play crucial roles. This review not only summarizes the current knowledge of Wnt signaling pathways in the regulation of skin development and governance of SCs during tissue homeostasis, but also discusses the potential crosstalk of Wnt signaling with other pathways involved in these processes. STEM CELLS 2018;36:22-35 SIGNIFICANCE STATEMENTThis review article provides a concise overview on the current knowledge of Wnt signaling pathways in the regulation of skin development, hair follicle morphogenesis, and governance of epidermal stem cells during tissue homeostasis. The spatial and temporal interconnections of Wnt/ß-catenin and ß-catenin-independent Wnt signaling in the developmental and homeostatic processes of skin are also highlighted. Using epidermal development and regeneration as examples, this study calls attention to the potential crosstalk between Wnt signaling with other pathways that co-orchestrate these processes.

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Axin2 marks quiescent hair follicle bulge stem cells that are maintained by autocrine Wnt/β-catenin signaling

Cited by 100 publications

References 43 publications

Blockade to pathological remodeling of infarcted heart tissue using a porcupine antagonist

Blockade to pathological remodeling of infarcted heart tissue using a porcupine antagonist

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

Concise Review: Wnt Signaling Pathways in Skin Development and Epidermal Stem Cells

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