Dermal Cell News Volume 5.11 | Apr 1 2019

TOP STORY

A Subset of TREM2⁺ Dermal Macrophages Secretes Oncostatin M to Maintain Hair Follicle Stem Cell Quiescence and Inhibit Hair Growth

Researchers showed that Oncostatin M (OSM), an IL-6 family cytokine, negatively regulated hair growth by signaling through JAK-STAT5 to maintain hair follicle stem cell (HFSC) quiescence. Genetic deletion of the OSM receptor or STAT5 could induce premature HFSC activation, suggesting that the resting telogen stage was actively maintained by the hair follicle niche. [Cell Stem Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Critical Role of ATP-P2X7 Axis in UV-Induced Melanogenesis

The authors demonstrated that extracellular adenosine 5’-triphosphate (ATP) released from keratinocytes by ultraviolet B radiation promoted melanin production in primary human epidermal melanocytes and ex vivo skin cultures. Intracellular calcium ion and protein kinase C/cAMP response element-binding protein signaling contributed to ATP-mediated melanogenesis. [J Invest Dermatol] Abstract | Graphical Abstract

TSLP Production Induced by Skin Irritation Results from the Concomitant Activation of PAR-2 and IL-1 Pathways

A combination of primary keratinocytes, skin explants and in vivo strategies was employed. Cells and explants were stimulated with IL-1 and PAR-2-Ag. Thymic stromal lymphopoietin (TSLP) levels were quantitated by ELISA and RT-qPCR. Chromatin immunoprecipitation and promoter reporter assays were employed to examine recruitment and functional activity of NF-kB at the TSLP promoter. [Br J Dermatol] Abstract

Metformin Induces the AP-1 Transcription Factor Network in Normal Dermal Fibroblasts

Primary human fibroblasts were treated in culture with metformin resulting in a significant decrease in cell proliferation without evidence of cell death. Furthermore, metformin induced repositioning of chromosomes 10 and 18 within the nuclear volume indicating altered genome organization. Transcriptome analyses from RNA sequencing datasets revealed that alteration in growth profiles and chromosome positioning occurred concomitantly with changes in gene expression profiles. [Sci Rep] Full Article

Melanocyte Chitosan/Gelatin Composite Fabrication with Human Outer Root Sheath-Derived Cells to Produce Pigment

Researchers isolated human hair follicle melanocyte stem cells (MelSCs) using “side population” to investigate their melanotic function. By analyzing mRNA expression of TYR, SOX10, and MITF, melanosome structure, and immunofluorescence with melanocyte-specific markers, they revealed that the SP-fraction contained MelSCs with an admixture of differentiated melanocytes. [Sci Rep] Full Article

SKIN CANCERS & DISORDERS

A Natural WNT Signaling Variant Potently Synergizes with Cdkn2ab Loss in Skin Carcinogenesis

ChIPseq analysis showed enrichment of H3K27-Ac, a mark for active enhancers, in the 5’ region of the Wnt7b 129P2 gene. The Wnt7b 129P2 allele appeared sufficient to cause in vitro transformation of Cdkn2ab-deficient cell lines primarily through CDK6 activation. [Nat Commun] Full Article

Cross-Talk between Receptor Tyrosine Kinases AXL and ERBB3 Regulates Invadopodia Formation in Melanoma Cells

Using a microscopy-based siRNA screen, scientists identified a series of regulators, the knock down of which either suppressed or enhanced invadopodia formation and function. Notably, the receptor tyrosine kinase AXL displayed a dual regulatory function, where both depletion or overexpression enhanced invadopodia formation and activity. [Cancer Res] Abstract | Full Article

MITF Expression Predicts Therapeutic Vulnerability to p300 Inhibition in Human Melanoma

Direct transcriptional control of microphthalmia-associated transcription factor (MITF) by p300-dependent histone acetylation within proximal gene regulatory regions was coupled to cellular proliferation, suggesting a significant growth regulatory axis. Further analysis revealed Forkhead Box M1 as a key effector of the p300-MITF axis driving cell growth that was selectively activated in human melanomas. [Cancer Res] Abstract | Full Article

TRIM44 Activates the AKT/mTOR Signal Pathway to Induce Melanoma Progression by Stabilizing TLR4

Gain- and loss-of-function experiments in cell lines and mouse xenograft models were performed to elucidate the function and underlying mechanisms of tripartite motif-containing protein 44 (TRIM44) induced tumor progression. Co-immunoprecipitation assays and mass spectrometric analyses were applied to verify the interacting proteins of TRIM44. [J Exp Clin Cancer Res] Full Article

USF1-Induced Upregulation of LINC01048 Promotes Cell Proliferation and Apoptosis in Cutaneous Squamous Cell Carcinoma by Binding to TAF15 to Transcriptionally Activate YAP1

Mechanistically, long intergenic non-protein coding RNA 1048 (LINC01048) was proved to be transcriptionally activated by USF1. Pathway analysis and western blot assay showed that knockdown of LINC01048 led to the activation of the Hippo pathway. Moreover, YAP1, a Hippo pathway factor, was positively regulated by LINC01048. [Cell Death Dis] Full Article

Eukaryotic Elongation Factor-2 Kinase Regulates the Cross-Talk between Autophagy and Pyroptosis in Doxorubicin-Treated Human Melanoma Cells In Vitro

Doxorubicin treatment activated autophagy in the melanoma cells; inhibition of autophagy by transfecting the cells with siRNA targeting Beclin1 or by pretreatment with chloroquine significantly augmented pyroptosis, thus sensitizing the melanoma cells to doxorubicin. [Acta Pharmacol Sin] Abstract

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Immunotherapy of Melanoma: Facts and Hopes

The hope and major challenge for the future is to understand the immunobiology of tumors with primary or acquired resistance to anti-PD-1 or anti-PD-1/anti-CTLA-4 and to develop effective immune therapies tailored to individual patient subsets not achieving long-term clinical benefit. [Clin Cancer Res] Abstract | Full Article

Skin Tissue Engineering: Wound Healing Based on Stem-Cell-Based Therapeutic Strategies

The authors present some sets of the data published on using embryonic stem cells, induced pluripotent stem cells, and adult stem cells in healing wounds. Additionally, they discuss the different angles whereby these cells can contribute to their unique features and show the current drawbacks. [Stem Cell Res Ther] Full Article

Visit our reviews page to see a complete list of reviews in the dermal cell research field.

Neon Therapeutics Presents Updated Data from Ongoing Phase Ib NT-001 Clinical Trial of Personal Neoantigen Vaccine NEO-PV-01

Neon Therapeutics, Inc. presented updated data describing the immune and pathologic markers associated with durable clinical benefit in patients enrolled in NT-001, an ongoing Phase Ib clinical trial evaluating NEO-PV-01 in combination with nivolumab. [Press release from Neon Therapeutics, Inc. discussing research presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

Study May Explain Why Immunotherapy Not Effective for Some Patients with Metastatic Melanoma and Kidney Cancer

White blood cells known as B cells have been shown to be effective for predicting which cancer patients will respond to immune checkpoint blockade therapy, according to a study at The University of Texas MD Anderson Cancer Center. [Press release from The University of Texas MD Anderson Cancer Center discussing research to be presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

SpinalCyte to Provide Clinical Trial Update

The presentation entitled, “Double Blind Placebo Controlled Clinical Trial of Universal Donor Fibroblast Product CybroCell™ for Treatment of Disc Degenerative Disease,” will include updates from SpinalCyte’s Phase I/II clinical trial for CybroCell™ including new 16-month data. [Press release from SpinalCyte, LLC discussing research to be presented at the 2019 International Society for the Advancement of Spine Surgery Annual Meeting (ISASS19), Anaheim] Press Release

PellePharm Initiates Pivotal Phase III Clinical Trial of Patidegib Topical Gel in Patients with Gorlin Syndrome

The Phase III study is intended to assess the safety and efficacy of patidegib topical gel for the reduction of disease burden of persistently developing basal cell carcinomas (BCCs) in Gorlin Syndrome, a rare genetic disease that leads to the chronic formation of multiple BCCs. [PellePharm, Inc. (Business Wire, Inc.)] Press Release

Fibrocell Announces Positive Feedback from Type B End-of-Phase II Meeting with FDA on Phase III Clinical Trial Design for FCX-007

Fibrocell Science, Inc. announced the completion of a Type B end-of-Phase II meeting with the FDA to discuss the design of a Phase III clinical trial for FCX-007, the company’s gene therapy candidate for the treatment of recessive dystrophic epidermolysis bullosa, to support a Biologics License Application filing. [Fibrocell Science, Inc.] Press Release

ASLAN Pharmaceuticals Completes First Part of Single Ascending Dose Study for ASLAN004 Targeting Atopic Dermatitis

ASLAN Pharmaceuticals announced the completion of the first part of the single ascending dose study testing the intravenous formulation of the first-in-class therapeutic antibody ASLAN004 in healthy volunteers. [ASLAN Pharmaceuticals] Press Release

PolarityTE Enrolls First Patients in Two Clinical Trials Evaluating SkinTE for the Treatment of Chronic Wounds

PolarityTE, Inc. announced that patient enrollment has begun for two new randomized controlled trials evaluating SkinTE™ for the treatment of chronic wounds, specifically diabetic foot ulcers and venous leg ulcers. [PolarityTE, Inc.] Press Release

AbbVie Announces First Regulatory Approval of SKYRIZI™ (Risankizumab) for the Treatment of Plaque Psoriasis, Generalized Pustular Psoriasis and Erythrodermic Psoriasis and Psoriatic Arthritis in Japan

AbbVie announced that the Japanese Ministry of Health, Labour and Welfare has approved SKYRIZI™, an interleukin-23 inhibitor, for the treatment of plaque psoriasis, generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis in adult patients who have an inadequate response to conventional therapies. [AbbVie Inc.] Press Release

EMA Grants PRIME Eligibility for KB103 to Treat Dystrophic Epidermolysis Bullosa

Krystal Biotech Inc. announced that the European Medicines Agency (EMA) has granted access to its PRIME (PRIority MEdicines) scheme for KB103, a first-in-class topical gene therapy for the treatment of dystrophic epidermolysis bullosa. Krystal’s application was supported by clinical data to date from the ongoing GEM-1 Phase I/II study coupled with non-clinical data. [Krystal Biotech Inc.] Press Release

ProQR Spins Out All Dystrophic Epidermolysis Bullosa Activities into Newly Formed Wings Therapeutics Created by EB Research Partnership

ProQR Therapeutics N.V. announced the strategic spin out of the Dystrophic Epidermolysis Bullosa (DEB) activities into the newly formed company, Wings Therapeutics. Wings Therapeutics will focus on developing therapies for DEB and continue to conduct clinical trials with QR-313 in exon 73 as well as progress other RNA molecules that are designed for other mutations that cause DEB. [ProQR Therapeutics N.V.] Press Release

What Thailand’s Long-Awaited Election Could Mean for Science

Thailand is bracing for the results of its first election since a military junta took charge in a 2014 coup. Scientists, like many other people in Thailand, want a more democratic country. But whether a pro-democracy party or a military-backed one ends up in charge, science is likely to prosper as a result of ongoing reforms put in place by the junta that are likely to continue under either government. [Nature News] Editorial

National Academy of Sciences Will Vote on Ejecting Sexual Harassers

The U.S. National Academy of Sciences in Washington, D.C., will ask its members this month to change the organization’s bylaws to allow proven sexual harassers and those guilty of other misconduct to be ejected from their ranks. That’s a first for the prestigious organization that advises the U.S. government on scientific issues: Its members, who are voted in by other members, have always been elected for life. [ScienceInsider] Editorial

NEW DASCS2019 Stem Cell Conference
May 2-3, 2019
Vejle, Denmark

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellowship – Epidermal Stem Cell Research (UC San Diego)

Postdoctoral Researcher – Immune-Epidermal Cell Stress Response (Queen Mary University of London)

Postdoctoral Fellowship – Immune Cell-Mediated Regulation (Hospital for Special Surgery)

Junior Faculty and Postdoctoral Positions – Epigenetic Regulation (Henry Ford Health System)

Postdoctoral Researcher – Skin Biology (University of Wisconsin-Madison)

Director – Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health)

Postdoctoral Scientist – Molecular Oncology (University of Manchester)

Research Assistant – Burn Research (Sunnybrook Health Sciences Centre)

Postdoctoral Fellowship – Tumor Immunology and Cancer Metabolism (Roswell Park Comprehensive Cancer Center)

PhD Position – Epidermal Tissue Mechanics (Forschungszentrum Jülich)

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