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| Open AccessApoptotic dysregulation mediates stem cell competition and tissue regeneration
The authors show that depletion of pro-apoptotic Bax protein bestows hair follicle stem cells with the capacity to eliminate viable neighboring cells by sequestration of TNFα, resulting in an increased stem cell pool, accelerated wound repair and de novo hair follicle regeneration.
- Marianna Yusupova
- , Roi Ankawa
- & Yaron Fuchs
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| Open AccessCyclical dermal micro-niche switching governs the morphological infradian rhythm of mouse zigzag hair
Biological rhythms influence physiology and morphogenesis, though how these influence periodic pattern formation remains unclear. Here the authors show that the infradian rhythm observed in zigzag hairs is regulated by hair progenitors and their micro-niche and influences hair shaft bending.
- Makoto Takeo
- , Koh-ei Toyoshima
- & Takashi Tsuji
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| Open AccessThy1 marks a distinct population of slow-cycling stem cells in the mouse epidermis
Koren and Feldman et al. report a distinct population of Thy1-expressing stem cells in the basal layer of the mouse epidermis. These stem cells do not compete neutrally and contribute long-term to both epidermal replenishment and wound repair.
- Elle Koren
- , Alona Feldman
- & Yaron Fuchs
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Article
| Open AccessROR2 regulates self-renewal and maintenance of hair follicle stem cells
Wnt signaling functions in tissue homeostasis and tumorigenesis. Here the authors show that ROR2, a Wnt receptor, plays roles not only in transducing Wnt signaling, but also in regulation of DNA damage response critical for stem cell maintenance.
- Anthony Veltri
- , Christopher M. R. Lang
- & Wen-Hui Lien
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Article
| Open AccessCDK9 activity switch associated with AFF1 and HEXIM1 controls differentiation initiation from epidermal progenitors
Epidermal progenitors are poised for differentiation, which allows for continual balance of self-renewal and differentiation. Here they show that the Super Elongation Complex regulates this process through direct regulation of a set of rapid response genes that involves a CDK9 activity switch.
- Sarah M. Lloyd
- , Daniel B. Leon
- & Xiaomin Bao
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Article
| Open AccessSpatially resolved proteomic map shows that extracellular matrix regulates epidermal growth
Ling Leng et al. construct a hierarchical skin proteome map and identify an extracellular matrix glycoprotein TGFBI, which is located in basement membrane and could enhance the growth and function of epidermal stem cells and promote wound healing.
- Jun Li
- , Jie Ma
- & Ling Leng
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Article
| Open AccessRN7SK small nuclear RNA controls bidirectional transcription of highly expressed gene pairs in skin
The noncoding RNA RN7SK regulates RNA polymerase II pausing and splicing. Here the authors deplete RN7SK in mouse and human during epidermal stem cell differentiation and reveal a novel role in orchestrating bidirectional transcription of highly expressed gene pairs.
- Roberto Bandiera
- , Rebecca E. Wagner
- & Michaela Frye
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Article
| Open AccessSingle-keratinocyte transcriptomic analyses identify different clonal types and proliferative potential mediated by FOXM1 in human epidermal stem cells
Epidermal cultures can treat skin diseases, such as Junctional Epidermolysis Bullosa, but the signature of stem cells is unclear. By single cell RNAseq analyses on human keratinocytes, the authors identify the molecular profile of holoclones and the role of FOXM1 in regulating the proliferative potential of epidermal stem cells.
- Elena Enzo
- , Alessia Secone Seconetti
- & Michele De Luca
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Article
| Open AccessMechanochemical control of epidermal stem cell divisions by B-plexins
It is unclear how epithelial tissues adjust cell division rates to cell density. Here, the authors show that Plexin-B1 and Plexin-B2 sense mechanical compression (crowding) of epidermal stem cells, resulting in inactivation of YAP and suppression of cell proliferation.
- Chen Jiang
- , Ahsan Javed
- & Thomas Worzfeld
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Article
| Open AccessSPT6 promotes epidermal differentiation and blockade of an intestinal-like phenotype through control of transcriptional elongation
The role of RNA polymerase II (Pol II) recruitment during adult stem cell differentiation is well understood, but not that of Pol II elongation. Here, the authors show that 30% of epidermal stem cell differentiation genes depend on SPT6 and PAF1 for Pol II elongation, and SPT6 loss leads to an intestine-like phenotype.
- Jingting Li
- , Xiaojun Xu
- & George L. Sen
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Article
| Open AccessTp63-expressing adult epithelial stem cells cross lineages boundaries revealing latent hairy skin competence
Adult stem cells are thought to be fate restricted to lineages distinct to their tissue of origin. Here, the authors demonstrate that Tp63 expressing epithelial stem cells from several disparate tissues can respond to skin morphogenetic signals and contribute to hair follicles, sebaceous glands and/or epidermis.
- Stéphanie Claudinot
- , Jun-Ichi Sakabe
- & Yann Barrandon
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Article
| Open AccessFgf and Wnt signaling interaction in the mesenchymal niche regulates the murine hair cycle clock
The underlying mechanisms regulating the mouse hair cycle remain poorly understood. Here, the authors find that Fgf and Wnt signaling pathways interact in the mesenchymal niche of the hair follicle to regulate the molecular clock that dictates the duration of hair growth.
- Sarina Harshuk-Shabso
- , Hila Dressler
- & David Enshell-Seijffers
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| Open AccessYAP1/TAZ-TEAD transcriptional networks maintain skin homeostasis by regulating cell proliferation and limiting KLF4 activity
Hippo TEAD-transcriptional regulators YAP1 and TAZ modulate cell growth, but the downstream networks are unclear. Here, the authors use a genetically-encoded inhibitor of YAP1/TAZ interaction with TEAD (TEADi) to disrupt transcriptional networks for cell cycle and terminal differentiation in human keratinocytes and mouse skin.
- Yao Yuan
- , Jeannie Park
- & Ramiro Iglesias-Bartolome
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Article
| Open AccessA novel mouse model demonstrates that oncogenic melanocyte stem cells engender melanoma resembling human disease
Currently, few mouse models exist to recapitulate human melanomagenesis. Here, the authors establish a c-Kit-CreER-driven model to target melanocyte stem cells (McSCs) and show that oncogenic McSCs give rise to epidermal melanoma that invade into the dermis, similar to human melanoma.
- Qi Sun
- , Wendy Lee
- & Mayumi Ito
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Article
| Open AccessIRF2 is a master regulator of human keratinocyte stem cell fate
Epidermal homeostasis requires long term stem cell function. Here, the authors apply transcriptional circuitry analysis based on integrated epigenomic profiling of primary human keratinocytes with high and low stem cell function to identify IRF2 as a negative regulator of stemness.
- Nicolas Mercado
- , Gabi Schutzius
- & Susan Kirkland
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Article
| Open AccessBlimp1+ cells generate functional mouse sebaceous gland organoids in vitro
The sebaceous gland (SG) has been proposed to be replenished by pools of cells, including a population in the SG base, marked by Blimp1. Here, the authors show that Blimp1+ cells can establish an organoid model of the SG, which is regulated by c-Myc and can recapitulate the early stages of acne vulgaris.
- Alona Feldman
- , Dzmitry Mukha
- & Yaron Fuchs
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Article
| Open AccessMechanical stretch induces hair regeneration through the alternative activation of macrophages
Mechanical stimulation is known to affect cell proliferation, differentiation, and regeneration. Here, the authors demonstrate that stretching mouse skin recruits macrophages and polarizes them into M2 cells that facilitate hair regeneration through the release of growth factors, including HGF and IGF-1
- Szu-Ying Chu
- , Chih-Hung Chou
- & Oscar K. Lee
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Article
| Open AccessBiologically relevant laminin as chemically defined and fully human platform for human epidermal keratinocyte culture
In vitro expansion of human epidermal keratinocytes to resurface severe wound defects still relies on a human/mouse xenograft culture system. Here the authors develop a fully human, xeno-free culture system using skin-associated laminins, normally present in vivo, to replace mouse feeder cells.
- Monica Suryana Tjin
- , Alvin Wen Choong Chua
- & Karl Tryggvason
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Article
| Open AccessJunB defines functional and structural integrity of the epidermo-pilosebaceous unit in the skin
Epidermal homeostasis is maintained by the activity of stem cells. Here, the authors show that deficiency of the transcription factor JunB leads to altered Notch signaling in stem cells, resulting in a cell fate switch and de novo formation of aberrant sebaceous glands, altered epidermal differentiation and impaired barrier function.
- Karmveer Singh
- , Emanuela Camera
- & Karin Scharffetter-Kochanek
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Article
| Open AccessFGF signalling controls the specification of hair placode-derived SOX9 positive progenitors to Merkel cells
Merkel cells are mechanoreceptors located in the epidermis whose developmental origin is unclear. Here the authors show that Merkel cells originate from SOX9 positive cells inside hair follicles and that FGFR2-mediated epithelial signalling is required for their specification.
- Minh Binh Nguyen
- , Idan Cohen
- & Elena Ezhkova
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Article
| Open AccessImmuno-detection by sequencing enables large-scale high-dimensional phenotyping in cells
Detecting proteins and post-translational modifications is important for drug screens, but the number of proteins measurable simultaneously is limited. Here the authors use antibodies tagged with DNA barcodes and high-throughput sequencing to detect up to 70 (phospho-)proteins in stem cells.
- Jessie A. G. van Buggenum
- , Jan P. Gerlach
- & Klaas W. Mulder
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Article
| Open AccessSpatial constraints govern competition of mutant clones in human epidermis
Deep sequencing technologies allow for the investigation of clonal evolution in human cancers. Here the authors, combining sequencing data from human skin with mathematical modelling and simulations, suggest that the spatial context of a mutation with respect to other mutant clones may lead to differential clonal evolution.
- M. D. Lynch
- , C. N. S. Lynch
- & F. M. Watt
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Article
| Open AccessTbx3-dependent amplifying stem cell progeny drives interfollicular epidermal expansion during pregnancy and regeneration
The abdominal skin expands rapidly during pregnancy. Here the authors show that a population of highly proliferative stem cell progenies expressing the transcription factor Tbx3 is required for abdominal skin expansion in pregnant mice.
- Ryo Ichijo
- , Hiroki Kobayashi
- & Fumiko Toyoshima
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Article
| Open AccessWNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation
Human WNT10A mutations are associated with dental defects and adult onset ectodermal dysplasia. Xuet al. show that WNT10A-activated ß-catenin plays dual roles in adult epithelial progenitor proliferation and differentiation by complexing with KLF4 in differentiating, but not proliferating, cells.
- Mingang Xu
- , Jeremy Horrell
- & Sarah E. Millar
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Article
| Open AccessYAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate
Notch signalling is a fundamental negative regulator of epidermal stemness. Here, the authors show that cell mechanics through YAP/TAZ activity prevent primary human keratinocytes from differentiating by inhibiting cell-autonomous Notch signals.
- Antonio Totaro
- , Martina Castellan
- & Stefano Piccolo
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Article
| Open AccessMacrophages induce AKT/β-catenin-dependent Lgr5+ stem cell activation and hair follicle regeneration through TNF
Hair can be regenerated after skin wounding. Here the authors show that inflammatory macrophages produce TNF that activates Wnt signalling in hair follicle stem cells to drive this hair regeneration after wound repair in mice.
- Xusheng Wang
- , Haiyan Chen
- & Yaojiong Wu
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Article
| Open AccessA genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells
Individual human epidermal cells differ in their self-renewal ability. Here the authors perform genome-wide pooled RNAi screens to uncover the molecular basis for this heterogeneity, and identify genes conferring a clonal growth advantage on normal and neoplastic human epidermal cells.
- Gernot Walko
- , Samuel Woodhouse
- & Fiona M. Watt
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Article
| Open AccessDefining stem cell dynamics and migration during wound healing in mouse skin epidermis
Wound healing is essential to repair the skin after injury and distinct stem cells in the epidermis are known to contribute to the process. Here the authors perform molecular, functional and clonal analysis and reveal the individual contribution of stem cells coming from different epidermal compartments to the wound-healing process in mice.
- Mariaceleste Aragona
- , Sophie Dekoninck
- & Cédric Blanpain