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Molecular Research of Epidermal Stem Cells 2017
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Molecular Research of Epidermal Stem Cells 2017

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (28 February 2018) | Viewed by 47919

Special Issue Editor

Dr. Miroslav Blumenberg

E-Mail Website
Guest Editor
Department of Dermatology, NYU School of Medicine, New York, NY, USA
Interests: molecular biology and genetics of human keratin genes; transcriptional profiling of skin cells using DNA microarrays; effects of UV light on skin; signal transduction in skin during inflammatory and proliferative processes; epidermal stem cells and differentiation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Arguably among the most exciting research areas, stem cell biology recently burst out with extraordinary thrill and promise. Because of its accessibility, epidermis was among the first organs targeted by stem cell researchers. Several crucial discoveries relating to stem cells biology originated in skin research, the origins of cancers, the influence of the niche, role in wound healing and use in gene replacement therapy, to name a few. The field is fast-moving, but sufficiently mature to warrant a special inclusive and comprehensive overview to define its range, challenges and future directions.

The goal of this special issue is to provide a summary of the field, describe its impact as well as introduce the recent advances in the Molecular Research of Epidermal Stem Cells. Both keratinocyte and melanocyte stem cells will be addressed, mainly those in the hair follicles, but the extrafollicular ones as well. This issue will address the markers of epidermal stem cells, the role of the niche, the regulatory processes governing quiescence and emergence into proliferation, epigenetics, interface of stem cells with cancer and wound healing, and their use in treating dermatologic disorders.

Dr. Miroslav Blumenberg
Guest Editor

Manuscript Submission Information

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Keywords

  • bulge region

  • cancer

  • epidermis

  • epigenetics

  • gene replacement therapy

  • hair

  • ichthyosis

  • melanocyte

  • niche

  • sebaceous gland

  • skin

  • wound healing

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Related Special Issues

Published Papers (7 papers)

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Research

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14 pages, 2629 KiB  
Article
Are the Effects of the Cholera Toxin and Isoproterenol on Human Keratinocytes’ Proliferative Potential Dependent on Whether They Are Co-Cultured with Human or Murine Fibroblast Feeder Layers?
by Sergio Cortez Ghio, Laurence Cantin-Warren, Rina Guignard, Danielle Larouche and Lucie Germain
Int. J. Mol. Sci. 2018, 19(8), 2174; https://doi.org/10.3390/ijms19082174 - 25 Jul 2018
Cited by 9 | Viewed by 4897
Abstract
Human keratinocyte culture has provided the means to treat burns, wounds and skin pathologies. To date, to efficiently culture keratinocytes, cells are cultured on an irradiated feeder layer (iFL), either comprising human (iHFL) or murine (i3T3FL) fibroblasts, and the culture medium is supplemented [...] Read more.
Human keratinocyte culture has provided the means to treat burns, wounds and skin pathologies. To date, to efficiently culture keratinocytes, cells are cultured on an irradiated feeder layer (iFL), either comprising human (iHFL) or murine (i3T3FL) fibroblasts, and the culture medium is supplemented with a cyclic adenosine monophosphate (cAMP) accumulation inducing agent such as isoproterenol (ISO) or cholera toxin (CT). Previous studies have characterized how the feeder layer type and the cAMP inducer type influence epithelial cells’ phenotype independently from one another, but it is still unknown if an optimal combination of feeder layer and cAMP inducer types exists. We used sophisticated statistical models to search for a synergetic effect of feeder layer and cAMP inducer types on human keratinocytes’ proliferative potential. Our data suggests that, when culturing human keratinocytes, using iHFL over i3T3FL increases population doublings and colony-forming efficiency through signaling pathways involving Ak mouse strain thymoma (Akt, also known as protein kinase B) isoforms 1 to 3, signal transducer and activator of transcription 5 (STAT5), p53, and adenosine monophosphate activated protein kinase α1 (AMPKα1). Both tested cAMP inducers ISO and CT yielded comparable outcomes. However, no significant synergy between feeder layer and cAMP inducer types was detected. We conclude that, to promote human keratinocyte growth in the early passages of culture, co-culturing them with a human feeder layer is preferable to a murine feeder layer. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2017)
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12 pages, 6293 KiB  
Article
2A-DUB/Mysm1 Regulates Epidermal Development in Part by Suppressing p53-Mediated Programs
by Christina Wilms, Ioanna Krikki, Adelheid Hainzl, Sonja Kilo, Marius Alupei, Evgenia Makrantonaki, Maximilian Wagner, Carsten M. Kroeger, Titus Josef Brinker and Martina Gatzka
Int. J. Mol. Sci. 2018, 19(3), 687; https://doi.org/10.3390/ijms19030687 - 28 Feb 2018
Cited by 12 | Viewed by 6612
Abstract
Development and homeostasis of the epidermis are governed by a complex network of sequence-specific transcription factors and epigenetic modifiers cooperatively regulating the subtle balance of progenitor cell self-renewal and terminal differentiation. To investigate the role of histone H2A deubiquitinase 2A-DUB/Mysm1 in the skin, [...] Read more.
Development and homeostasis of the epidermis are governed by a complex network of sequence-specific transcription factors and epigenetic modifiers cooperatively regulating the subtle balance of progenitor cell self-renewal and terminal differentiation. To investigate the role of histone H2A deubiquitinase 2A-DUB/Mysm1 in the skin, we systematically analyzed expression, developmental functions, and potential interactions of this epigenetic regulator using Mysm1-deficient mice and skin-derived epidermal cells. Morphologically, skin of newborn and young adult Mysm1-deficient mice was atrophic with reduced thickness and cellularity of epidermis, dermis, and subcutis, in context with altered barrier function. Skin atrophy correlated with reduced proliferation rates in Mysm1−/− epidermis and hair follicles, and increased apoptosis compared with wild-type controls, along with increases in DNA-damage marker γH2AX. In accordance with diminished α6-Integrinhigh+CD34+ epidermal stem cells, reduced colony formation of Mysm1−/− epidermal progenitors was detectable in vitro. On the molecular level, we identified p53 as potential mediator of the defective Mysm1-deficient epidermal compartment, resulting in increased pro-apoptotic and anti-proliferative gene expression. In Mysm1−/−p53−/− double-deficient mice, significant recovery of skin atrophy was observed. Functional properties of Mysm1−/− developing epidermis were assessed by quantifying the transepidermal water loss. In summary, this investigation uncovers a role for 2A-DUB/Mysm1 in suppression of p53-mediated inhibitory programs during epidermal development. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2017)
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743 KiB  
Communication
Impact of Platelet-Rich Plasma on Viability and Proliferation in Wound Healing Processes after External Radiation
by Yvonne Reinders, Oliver Felthaus, Gero Brockhoff, Fabian Pohl, Norbert Ahrens, Lukas Prantl and Frank Haubner
Int. J. Mol. Sci. 2017, 18(8), 1819; https://doi.org/10.3390/ijms18081819 - 22 Aug 2017
Cited by 17 | Viewed by 5746
Abstract
Platelet-rich plasma is a current subject of studies on chronic wound healing therapy due to possible pro-angiogenic effects. Microvascular compromise represents the major component in radiogenic wound healing complications. The effects of platelet-rich plasma on irradiated cells of the cutaneous wound healing process [...] Read more.
Platelet-rich plasma is a current subject of studies on chronic wound healing therapy due to possible pro-angiogenic effects. Microvascular compromise represents the major component in radiogenic wound healing complications. The effects of platelet-rich plasma on irradiated cells of the cutaneous wound healing process are poorly understood so far. In this study, the interaction of endothelial cells and adipose-derived stem cells in conjunction with treatment with platelet-rich plasma is investigated in the context of radiation effects. Therefore, the expression of surface-marker CD90 and CD31 was determined. Moreover, cell proliferation and viability after external radiation was analyzed with and without treatment by platelet-rich plasma. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2017)
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8246 KiB  
Article
The Co-Expression Pattern of p63 and HDAC1: A Potential Way to Disclose Stem Cells in Interfollicular Epidermis
by Jung-Won Shin, Hye-Ryung Choi, Kyung-Mi Nam, Hyun-Sun Lee, Sung-Ae Kim, Hyun-Jae Joe, Toyama Kazumi and Kyoung-Chan Park
Int. J. Mol. Sci. 2017, 18(7), 1360; https://doi.org/10.3390/ijms18071360 - 26 Jun 2017
Cited by 12 | Viewed by 5440
Abstract
Stem cell markers of interfollicular epidermis (IEF) have not been established thus far. The aim of this study is to suggest a new way to disclose IFE-stem cells by combining the expression of histone deacetylases (HDAC) 1 and p63. Immunohistochemical staining of HDAC1 [...] Read more.
Stem cell markers of interfollicular epidermis (IEF) have not been established thus far. The aim of this study is to suggest a new way to disclose IFE-stem cells by combining the expression of histone deacetylases (HDAC) 1 and p63. Immunohistochemical staining of HDAC1 and p63 was performed in six normal human samples. Moreover, a skin equivalent (SE) model was treated with suberoylanilohydroxamic acid (SAHA, an HDAC inhibitor) to elucidate the role of HDAC1. Finally, rapidly adhering (RA) keratinocytes to a type IV collagen, which have been identified to represent epidermal stem cells, were subjected to Western blot analysis with antibodies against HDAC1. In normal samples, there was a minor subpopulation comprised of p63-positive and HDAC1-negative cells in the basal layers. The proportion of this subpopulation was decreased with age. In the SE model, SAHA treatment increased the epidermal thickness and number of p63-positive cells in a dose dependent manner. After SAHA treatment, the expression of differentiation markers was decreased, while that of basement membrane markers was increased. In a Western blot analysis, HDAC1 was not expressed in RA cells. In conclusion, the combination of p63-positive and HDAC1-negative expressions can be a potential new way for distinguishing epidermal stem cells. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2017)
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Review

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15 pages, 349 KiB  
Review
Extracellular Matrix as a Regulator of Epidermal Stem Cell Fate
by Elina Chermnykh, Ekaterina Kalabusheva and Ekaterina Vorotelyak
Int. J. Mol. Sci. 2018, 19(4), 1003; https://doi.org/10.3390/ijms19041003 - 27 Mar 2018
Cited by 60 | Viewed by 8103
Abstract
Epidermal stem cells reside within the specific anatomic location, called niche, which is a microenvironment that interacts with stem cells to regulate their fate. Regulation of many important processes, including maintenance of stem cell quiescence, self-renewal, and homeostasis, as well as the regulation [...] Read more.
Epidermal stem cells reside within the specific anatomic location, called niche, which is a microenvironment that interacts with stem cells to regulate their fate. Regulation of many important processes, including maintenance of stem cell quiescence, self-renewal, and homeostasis, as well as the regulation of division and differentiation, are common functions of the stem cell niche. As it was shown in multiple studies, extracellular matrix (ECM) contributes a lot to stem cell niches in various tissues, including that of skin. In epidermis, ECM is represented, primarily, by a highly specialized ECM structure, basement membrane (BM), which separates the epidermal and dermal compartments. Epidermal stem cells contact with BM, but when they lose the contact and migrate to the overlying layers, they undergo terminal differentiation. When considering all of these factors, ECM is of fundamental importance in regulating epidermal stem cells maintenance, proper mobilization, and differentiation. Here, we summarize the remarkable progress that has recently been made in the research of ECM role in regulating epidermal stem cell fate, paying special attention to the hair follicle stem cell niche. We show that the destruction of ECM components impairs epidermal stem cell morphogenesis and homeostasis. A deep understanding of ECM molecular structure as well as the development of in vitro system for stem cell maintaining by ECM proteins may bring us to developing new approaches for regenerative medicine. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2017)
1517 KiB  
Review
The Role of p16INK4a Pathway in Human Epidermal Stem Cell Self-Renewal, Aging and Cancer
by Daniela D’Arcangelo, Lavinia Tinaburri and Elena Dellambra
Int. J. Mol. Sci. 2017, 18(7), 1591; https://doi.org/10.3390/ijms18071591 - 22 Jul 2017
Cited by 51 | Viewed by 11216
Abstract
The epidermis is a self-renewing tissue. The balance between proliferation and differentiation processes is tightly regulated to ensure the maintenance of the stem cell (SC) population in the epidermis during life. Aging and cancer may be considered related endpoints of accumulating damages within [...] Read more.
The epidermis is a self-renewing tissue. The balance between proliferation and differentiation processes is tightly regulated to ensure the maintenance of the stem cell (SC) population in the epidermis during life. Aging and cancer may be considered related endpoints of accumulating damages within epidermal self-renewing compartment. p16INK4a is a potent inhibitor of the G1/S-phase transition of the cell cycle. p16INK4a governs the processes of SC self-renewal in several tissues and its deregulation may result in aging or tumor development. Keratinocytes are equipped with several epigenetic enzymes and transcription factors that shape the gene expression signatures of different epidermal layers and allow dynamic and coordinated expression changes to finely balance keratinocyte self-renewal and differentiation. These factors converge their activity in the basal layer to repress p16INK4a expression, protecting cells from senescence, and preserving epidermal homeostasis and regeneration. Several stress stimuli may activate p16INK4a expression that orchestrates cell cycle exit and senescence response. In the present review, we discuss the role of p16INK4a regulators in human epidermal SC self-renewal, aging and cancer. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2017)
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1030 KiB  
Review
Long-Lived Epidermal Cancer-Initiating Cells
by Marina Youssef, Andrew Cuddihy and Charbel Darido
Int. J. Mol. Sci. 2017, 18(7), 1369; https://doi.org/10.3390/ijms18071369 - 27 Jun 2017
Cited by 11 | Viewed by 5186
Abstract
Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population, as well as an economic load to the health care system; yet treatments of these preventable cancers remain ineffective. Studies estimate [...] Read more.
Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population, as well as an economic load to the health care system; yet treatments of these preventable cancers remain ineffective. Studies estimate that there has been a 2-fold increase in the incidence of NMSCs between the 1960s and 1980s. The increase in cases of NMSCs, as well as the lack of effective treatments, makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgently required. Research over the past few years has provided data supporting both a “bottom up” and “top down” mechanism of tumourigenesis. The “bottom up” concept involves a cancer stem cell originating in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. The “top down” concept involves a more differentiated cell undergoing genetic modifications leading to dedifferentiation, giving rise to cancer initiating cells (CICs). This review explores both concepts, to paint a picture of the skin SCC cell of origin, the underlying biology, and also how this knowledge might be exploited to develop novel therapies. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2017)
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