Balancing Stem Cell Self Renewal And Differentiation In The Skin

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Balancing Stem Cell Self Renewal And Differentiation In The Skin

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Author : Xinhong Lim
language : en
Publisher:
Release Date : 2013

Balancing Stem Cell Self Renewal And Differentiation In The Skin written by Xinhong Lim and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with categories.

The skin is a classical example of a tissue maintained by stem cells, but the identity of the stem cells that maintain the different epidermal compartments and the signaling mechanisms that control their activity remain unclear. Using lineage tracing and quantitative clonal analyses, we show that the Wnt-target gene Axin2 marks epidermal stem cells that compete neutrally and require Wnt/[beta]-catenin signaling to proliferate. By RNA in situ hybridization, we show that the Axin2-expressing stem cells produce their own self-renewal signals in the form of Wnt proteins. These cells also express secreted Wnt inhibitors, including Dkks, which accumulate at high levels around more differentiated cells. We propose a new model for skin maintenance, in which epidermal stem cells produce short-range Wnt signals to maintain their own identity and function, while simultaneously secreting longer-range inhibitors that suppress Wnt signaling to promote differentiation of the stem cell progeny.

Myc Transcriptional Functions Controlling Epidermal Stem Cell Self Renewal And Differentiation

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Author : Elisabete Nascimento
language : en
Publisher:
Release Date : 2011

Myc Transcriptional Functions Controlling Epidermal Stem Cell Self Renewal And Differentiation written by Elisabete Nascimento and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.

The oncoprotein MYC has long been recognized as an important stem cell regulator, yet its direct biological contributions have been difficult to determine. MYC activation can induce pleiotropic phenotypes and mediates cellular functions as opposing as cell growth and proliferation, metabolism, differentiation and apoptosis. In addition, functional redundancy with MYCL and MYCN proteins as well as dose dependency, complicates the identification of the most relevant biological functions. Studies in tissues with high proliferative capacity and rapid turnover have shown that MYC is a key regulator of homeostasis by balancing stem cell self-renewal, proliferation and differentiation processes. In skin, MYC induces the exit of epidermal stem cells from their niche, increases proliferation of progenitor cells and subsequently stimulates lineage specific differentiation into interfollicular epidermis and sebaceous glands; yet the direct transcriptional roles of MYC in these processes remained elusive. To gain insight into the transcriptional roles of MYC in epidermal stem cell homeostasis, I performed chromatin immunoprecipitation on microarrays (ChIP-on-Chip) using mouse proximal promoter arrays combined with mRNA expression data that was generated using epidermal cells from wild-type and transgenic K14MycER mice, treated in a time-course from zero to six days with tamoxifen, to induce the?Myc? transgene expression in the basal undifferentiated layers of the epidermis. Data analysis revealed that 2187 genes, which corresponds to 15% of the promoter regions covered, were directly regulated by MYC. To identify genes uniquely regulated by MYC in skin, I performed gene expression studies on mouse skin in which MYC was conditionally deleted in the basal layer of the epidermis. Remarkably, I found that 45% of all repressed genes were related to epidermal maintenance and differentiation. To better understand the mechanism of how MYC induces keratinocytes to differentiate specifically into lineages of sebaceous glands and interfollicular epidermis, I analyzed whether MYC might have directly regulated genes involved in skin differentiation. Here, I focused my studies on a single 2.2 Mb locus located on mouse chromosome 3 designated as the epidermal differentiation complex (EDC). To assess how activation of MYC could influence the expression of genes localized to the EDC, I performed ChIP-on-Chip for MYC, H3K4me3, H3K27me3, as well as transcription factors, which have been described to regulate terminal differentiation in skin, such as CEBP?, OVOL-1, KLF4, TCFAP2-? and SIN3A, among others. I demonstrated that MYC recruits a specific set of tissue-specific transcription factors to the EDC, (e.g. KLF4 and OVOL-1) and thereby prevents binding of a different and distinct set of genomic regulators, (e.g. CEBP?, MXI1 and SIN3A). Using a combination of mouse models and systems biology tools, I then identified SIN3A as a key regulator in this MYC-dependent transcriptional network. I found that MYC and SIN3A form a negative feedback loop, which is required to balance proliferation and differentiation in epidermis, and both factors are essential to maintain skin homeostasis.

Stem Cell Proliferation And Differentiation

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Author :
language : en
Publisher: Academic Press
Release Date : 2020-03-24

Stem Cell Proliferation And Differentiation written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-03-24 with Science categories.

Stem Cell Proliferation and Differentiation, Volume 138, the latest release in the Current Topics in Developmental Biology series, highlights new advances in the field, with this new volume presenting interesting chapters. Each chapter is written by an international board of authors. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Current Topics in Developmental Biology series Includes the latest information on stem cell proliferation and differentiation

Stem Cells Handbook

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Author : Stewart Sell
language : en
Publisher: Springer Science & Business Media
Release Date : 2003-10-22

Stem Cells Handbook written by Stewart Sell and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2003-10-22 with Medical categories.

The power of stem cells for tissue development, regeneration, and renewal has been well known by embryologists and developmental biologists for many years. Those presently active in research in the stem cell field owe much to previous work by embryologists and cancer researchers for their insights into what stem cells can do. In the last 4- 5 years, the rapid expansion of the concept of adult tissue stem cells as pluripotent progenitors for various tissues has led to an even greater appreciation of the power of stem cells. The demonstration that both embryonic and adult tissue stem cells have the ability to produce progenitor cells for tissue renewal has opened vast possibilities for treatment of congenital deficiency diseases as well as for regeneration of damaged tissues. Older concepts of determination leading to loss of potential during differentiation of adult tissues are being replaced by newer ideas that cells with multiple potential exist in different forms in various adult organs and that cells thought to be restricted to differentiation to one cell type may be able to "transdifferentiate" into other tissue cell types. Thus, the concept of "embryonic rests" in adult tissues, hypothesized to be the cellular origin of cancer by Durante and Conheim in the 1870s, now can be expanded to include survival of pluripotential embryonic-like stem cells in adult tissues.

Regulatory Networks In Stem Cells

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Author : Vinagolu K. Rajasekhar
language : en
Publisher: Springer Science & Business Media
Release Date : 2009-03-04

Regulatory Networks In Stem Cells written by Vinagolu K. Rajasekhar and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-03-04 with Medical categories.

Stem cells appear to be fundamental cellular units associated with the origin of multicellular organisms and have evolved to function in safeguarding the cellular homeostasis in organ t- sues. The characteristics of stem cells that distinguish them from other cells have been the fascinating subjects of stem cell research. The important properties of stem cells, such as ma- tenance of quiescence, self-renewal capacity, and differentiation potential, have propelled this exciting ?eld and presently form a common theme of research in developmental biology and medicine. The derivation of pluripotent embryonic stem cells, the prospective identi?cation of multipotent adult stem cells, and, more recently, the induced pluripotent stem cells (popularly called iPS) are important milestones in the arena of stem cell biology. Complex networks of transcription factors, different signaling molecules, and the interaction of genetic and epi- netic events constantly modulate stem cell behavior to evoke programming and reprogramming processes in normal tissue homeostasis during development. In any given cellular scenario, the regulatory networks can pose considerable complexity and yet exert an orderly control of stem cell differentiation during normal development. An aberration in these ?nely tuned processes during development usually results in a spectrum of diseases such as cancers and neurological disorders. Thisunderscorestheimminentneedforamorecompleteunderstandingofmolecular mechanisms underlying the regulatory circuitries required for stem cell maintenance. Overthepast3–5years,adiversegroupofbenchandphysicianscientistshaveprospectively enhanced our knowledge of stem cell biology. These studies are unveiling many unrecognized or previously unknown fundamentals of developmental biology.

Stem Cells Between Regeneration And Tumorigenesis

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Author : Monica Neagu
language : en
Publisher: Bentham Science Publishers
Release Date : 2016-09-16

Stem Cells Between Regeneration And Tumorigenesis written by Monica Neagu and has been published by Bentham Science Publishers this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-09-16 with Science categories.

Experts in the field of cellular biology have shown that the reactivation of pluripotency inherent in all cells can allow us to reprogram cells into a specific cell line. This reprogramming paradigm is steadily enhancing our understanding of cell differentiation processes and cellular identity. Consequently, new prospects for cellular therapies of diseases and in vivo regeneration have risen. Stem Cells Between Regeneration and Tumorigenesis focuses on organ specific molecular pathways that trigger two opposite ways that a stem cell can grow (regeneration and neoplasia). Chapters provide a balanced set of information about tissue regeneration and tumorigenesis in several tissues and biological systems (the nervous, circulatory, oral, skin, digestive and endocrine systems). Additional reviews of the immunological role in regulating the two stem cell growth processes and the role of genomics and proteomics in understanding these processes round up the contents of this monograph. Readers of this book will gain the following key benefits: -an insight into the complexity and controversy surrounding the established dual stem cell behavior paradigm (regeneration versus tumorigenesis) -an understanding of the intricate cellular processes such as stem cells maintenance -background knowledge of optimizing tailored therapy in personalized and regenerative medicine Stem Cells Between Regeneration and Tumorigenesis is a useful resource for advanced graduates and researchers undertaking courses in molecular biology and personalized medicine, as well as interns involved in stem cell research programs.

Embryonic Stem Cells

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Author : Michael S. Kallos
language : en
Publisher: BoD – Books on Demand
Release Date : 2011-10-12

Embryonic Stem Cells written by Michael S. Kallos and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-10-12 with Science categories.

The ultimate clinical implementation of embryonic stem cells will require methods and protocols to turn these unspecialized cells into the fully functioning cell types found in a wide variety of tissues and organs. In order to achieve this, it is necessary to clearly understand the signals and cues that direct embryonic stem cell differentiation. This book provides a snapshot of current research on the differentiation of embryonic stem cells to a wide variety of cell types, including neural, cardiac, endothelial, osteogenic, and hepatic cells. In addition, induced pluripotent stem cells and other pluripotent stem cell sources are described. The book will serve as a valuable resource for engineers, scientists, and clinicians as well as students in a wide range of disciplines.

Regulatory Networks In Stem Cells

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Author : Vinagolu K. Rajasekhar
language : en
Publisher: Humana Press
Release Date : 2009-03-19

Regulatory Networks In Stem Cells written by Vinagolu K. Rajasekhar and has been published by Humana Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-03-19 with Medical categories.

Stem cells appear to be fundamental cellular units associated with the origin of multicellular organisms and have evolved to function in safeguarding the cellular homeostasis in organ t- sues. The characteristics of stem cells that distinguish them from other cells have been the fascinating subjects of stem cell research. The important properties of stem cells, such as ma- tenance of quiescence, self-renewal capacity, and differentiation potential, have propelled this exciting ?eld and presently form a common theme of research in developmental biology and medicine. The derivation of pluripotent embryonic stem cells, the prospective identi?cation of multipotent adult stem cells, and, more recently, the induced pluripotent stem cells (popularly called iPS) are important milestones in the arena of stem cell biology. Complex networks of transcription factors, different signaling molecules, and the interaction of genetic and epi- netic events constantly modulate stem cell behavior to evoke programming and reprogramming processes in normal tissue homeostasis during development. In any given cellular scenario, the regulatory networks can pose considerable complexity and yet exert an orderly control of stem cell differentiation during normal development. An aberration in these ?nely tuned processes during development usually results in a spectrum of diseases such as cancers and neurological disorders. Thisunderscorestheimminentneedforamorecompleteunderstandingofmolecular mechanisms underlying the regulatory circuitries required for stem cell maintenance. Overthepast3–5years,adiversegroupofbenchandphysicianscientistshaveprospectively enhanced our knowledge of stem cell biology. These studies are unveiling many unrecognized or previously unknown fundamentals of developmental biology.

Bmi1 Regulates Self Renewal And Differentiation Of Human Mesenchymal Stem Cells

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Author : Yun Joon Jung
language : en
Publisher:
Release Date : 2011

Bmi1 Regulates Self Renewal And Differentiation Of Human Mesenchymal Stem Cells written by Yun Joon Jung and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.

One of the central questions in stem cell biology is to understand how stem cells regulate self-renewal and differentiation. Recently, polycomb group (PcG) proteins have been associated with the regulation of adult stem cells. BMI1, a constituent of PcG proteins, is known to be required for self-renewal in many tissues but its role in mesenchymal stem cells (MSCs) remains to be illustrated. Here, loss-of-function and gain-of-functions analysis in MSCs point out that BMI1 is critical for the MSC self-renewal and cell fate decision. Knockdown of BMI1 prevents cell proliferation induced by p14ARF/p16INK4A and increases apoptosis. Gain of functions analysis reveals that overexpression of BMI1 reduces apoptosis and increases cell proliferation by repressing p14ARF/p16INK4A. In addition, BMI1 is crucial for regulation of the multipotency of MSCs. Loss of BMI1 resulted in reduction in MSC differentiation potential due to cell cycle inhibition. Overexpression of BMI1 caused repression of transcripts of differentiation-related genes, RUNX2 and PPAR[gamma], in osteogenesis and adipogenesis, respectively. Thus, reduced expression of these genes leads to decreased differentiation potential in MSCs. My data, therefore, suggests that BMI1 regulates the self-renewal of MSCs.

Essentials Of Stem Cell Biology

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Author : Robert Lanza
language : en
Publisher: Academic Press
Release Date : 2009-06-05

Essentials Of Stem Cell Biology written by Robert Lanza and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-06-05 with Science categories.

First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists, researchers, practitioners and students that are embracing the latest advances in stem cells. Representing the combined effort of seven editors and more than 200 scholars and scientists whose pioneering work has defined our understanding of stem cells, this book combines the prerequisites for a general understanding of adult and embryonic stem cells with a presentation by the world's experts of the latest research information about specific organ systems. From basic biology/mechanisms, early development, ectoderm, mesoderm, endoderm, methods to application of stem cells to specific human diseases, regulation and ethics, and patient perspectives, no topic in the field of stem cells is left uncovered. Selected for inclusion in Doody's Core Titles 2013, an essential collection development tool for health sciences libraries Contributions by Nobel Laureates and leading international investigators Includes two entirely new chapters devoted exclusively to induced pluripotent stem (iPS) cells written by the scientists who made the breakthrough Edited by a world-renowned author and researcher to present a complete story of stem cells in research, in application, and as the subject of political debate Presented in full color with glossary, highlighted terms, and bibliographic entries replacing references