Growing evidence suggests that epigenetic mechanisms play a central role in stem cell biology and are vital for determining gene expression during cellular differentiation and governing mammalian development. In Stem Cell Epigenetics, leading international researchers examine how chromatin regulation and bona fide epigenetic mechanisms underlie stem cell renewal and differentiation. Authors also explore how the diversity of cell types, including the extent revealed by single cell omic approaches, is achieved, and how such processes may be reversed or managed via epigenetic reprogramming. Topics discussed include chromatin in pluripotency, stem cells and DNA methylation, histone modifications in stem cells and differentiation, higher-order chromatin conformation in pluripotent cells, stem cells and cancer, epigenetics and disease modeling, brain organoids from pluripotent cells, transcriptional regulation in stem cells and differentiation, non-coding RNAs in pluripotency and early differentiation, and diseases caused by epigenetic alterations in stem cells. Additionally, the book discusses the potential implementation of stem cell epigenetics in drug discovery, regenerative medicine, and disease treatment. Stem Cell Epigenetics will provide researchers and physicians with a state-of-the-art map to orient across the frontiers of this fast-evolving field. Analyzes the role of epigenetics in embryonic stem cell regulation Indicates the epigenetic mechanisms involved in stem cell differentiation and highlights modifications and misregulations that may result in disease pathogenesis Examines the potential applications of stem cell epigenetics in therapeutic disease interventions and regenerative medicine, providing a foundation for researchers and physicians to bring this exciting and fast-evolving field into a clinical setting Features chapter contributions by leading international experts

Stem Cell Epigenetics, Volume 16, examines how epigenetics are involved in stem cell differentiation, how a stem cell rapidly transitions into a molecularly distinct cell type, and how this process may be reversed or managed via epigenetic reprogramming. Topics discussed include chromatin in pluripotency, epigenetic regulation of reprogramming, stem cells and DNA methylation, histone modifications in stem cells and differentiation, higher-order chromatin conformation in pluripotent cells, epigenetics and disease modeling, organoids from pluripotent cells, transcriptional regulation in stem cells and differentiation, non-coding RNAs in pluripotency and early differentiation, and diseases caused by epigenetic alterations in stem cells. Additionally, the potential implementation of stem cell epigenetics in drug discovery, regenerative medicine, and disease treatment is discussed in detail, helping researchers and physicians bring this exciting and fast evolving field to the clinic. Provides genetic researchers, students and physicians with evidence indicating the epigenetic mechanisms involved in stem cell differentiation Highlights the specific characteristics of the epigenetic modifications and misregulations that may result in disease pathogenesis Examines the potential application of stem cell epigenetics towards developing therapeutic interventions for disease and advancing regenerative medicine Features chapter contributions by leading international experts

The ability of a single genome to give rise to hundreds of functionally distinct cell type programs is in itself remarkable. Pioneering studies over the past few decades have demonstrated that this plasticity is retained throughout development, a phenomenon of epigenetic programming and reprogramming that remains one of the most fascinating areas of modern biology, with major relevance to human health and disease. This book presents the basic biology involved, including key mechanistic insights into this rapidly growing field.

Studies have shown that alterations of epigenetics and microRNAs (miRNAs) play critical roles in the initiation and progression of human cancer. Epigenetic silencing of tumor suppressor genes in cancer cells is generally mediated by DNA hypermethylation of CpG island promoter and histone modification such as methylation of histone H3 lysine 9 (H3K9) and tri-methylation of H3K27. MiRNAs are small non-coding RNAs that regulate expression of various target genes. Specific miRNAs are aberrantly expressed and play roles as tumor suppressors or oncogenes during carcinogenesis. Important tumor suppressor miRNAs are silenced by epigenetic alterations, resulting in activation of target oncogenes in human malignancies. Stem cells have the ability to perpetuate themselves through self-renewal and to generate mature cells of various tissues through differentiation. Accumulating evidence suggests that a subpopulation of cancer cells with distinct stem-like properties is responsible for tumor initiation, invasive growth, and metastasis formation, which is defined as cancer stem cells. Cancer stem cells are considered to be resistant to conventional chemotherapy and radiation therapy, suggesting that these cells are important targets of cancer therapy. DNA methylation, histone modification and miRNAs may be deeply involved in stem-like properties in cancer cells. Restoring the expression of tumor suppressor genes and miRNAs by chromatin modifying drugs may be a promising therapeutic approach for cancer stem cells. In this Research Topic, we discuss about alterations of epigenetics and miRNAs in cancer and cancer stem cell and understand the molecular mechanism underlying the formation of cancer stem cell, which may provide a novel insight for treatment of refractory cancer.

This textbook covers the basic aspects of stem cell research and applications in regenerative medicine. Each chapter includes a didactic component and a practical section. The book offers readers insights into: How to identify the basic concepts of stem cell biology and the molecular regulation of pluripotency and stem cell development. How to produce induced pluripotent stem cells (iPSCs) and the basics of transfection. The biology of adult stem cells, with particular emphasis on mesenchymal stromal cells and hematopoietic stem cells, and the basic mechanisms that regulate them. How cancer stem cells arise and metastasize, and their properties. How to develop the skills needed to isolate, differentiate and characterize adult stem The clinical significance of stem cell research and the potential problems that need to be overcome. Evaluating the use of stem cells for tissue engineering and therapies (the amniotic membrane) The applications of bio-nanotechnology in stem cell research. How epigenetic mechanisms, including various DNA modifications and histone dynamics, are involved in regulating the potentiality and differentiation of stem cells. The scientific methods, ethical considerations and implications of stem cell research.

This indispensable volume highlights recent studies identifying epigenetic mechanisms as essential regulators of skin development, stem cell activity and regeneration. Chapters are contributed by leading experts and promote the skin as an accessible model system for studying mechanisms that control organ development and regeneration. The timely discussions contained throughout are of broad relevance to other areas of biology and medicine and can help inform the development of novel therapeutics for skin disorders as well as new approaches to skin regeneration that target the epigenome. Part of the highly successful Stem Cells and Regenerative Medicine series, Epigenetic Regulation of Skin Development and Regeneration uncovers the fundamental significance of epigenetic mechanisms in skin development and regeneration, and emphasizes the development of new therapies for a number of skin disorders, such as pathological conditions of epidermal differentiation, pigmentation and carcinogenesis. At least six categories of researchers will find this book essential, including stem cell, developmental, hair follicle or molecular biologists, and gerontologists or clinical dermatologists.

The regulatory capacities of epigenetic mechanisms including DNA methylation, histone modifications, and non-coding RNAs, have seen a rising interest in recent years. These epigenetic marks are pervasive and non-randomly distributed across the genome, raising intriguing questions on how epigenetics contributes to genomic features that define cellular identity and function. Unlike fixed genetic information that is shared between all cell types, epigenetics involve multiple layers of regulation and can vary dramatically across different cell types and genomic contexts. Thus, much more effort is required to procure a complete perspective of the manifold epigenetic landscape. The body of work in this dissertation focuses on epigenetic studies in the mammalian pluripotent stem cell model system. We utilize high-throughput technologies such as microarrays and next-generation sequencing (NGS) as well as leverage existing epigenetic maps to address a wide range of molecular questions on a comprehensive global scale. This dissertation is organized into three overarching themes: First, we employed genome-wide gene expression and DNA methylation profiling tools to determine whether different cell types display unique biomarkers that can be used to distinguish them from other cell types (Chapters 2-5). We found that human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) carry distinct features in both gene expression and DNA methylation patterns, arguing in favor of the idea that these two pluripotent cell types are different. Furthermore, we compared pluripotent stem cell derived retinal pigmented epithelium (hESC-RPE and hiPSC-RPE) with fetal and adult RPE and found that all RPE cells share a core set of signature genes that distinguishes them from all other cell types. We propose these signature genes will be useful for evaluating the quality of stem-cell derived RPE. Finally, novel corneal endothelial cells (CECs) biomarkers were identified through comparing 12 other tissue types, paving the way for future studies to evaluate properties of stem-cell derived CECs. We next examined how molecular features of pluripotent stem cells are altered during the differentiation process of stem cells (Chapters 6-8). Using the RPE differentiation paradigm, we profiled both microRNA and DNA methylation patterns in intermediate stages between pluripotent stem cells and mature RPE. These two separate studies identified subsets of dynamically regulated epigenetic marks, some of which are associated with RPE signature gene expression. Furthermore, we used a highly innovative and powerful single-cell RNA-sequencing approach to profile transcriptional changes in the early embryo beginning from mature oocyte to morula stages. This study identified a conserved genetic program describing a highly dynamic transcriptional architecture during early embryogenesis. Finally, we took a focused analysis on how DNA methyltransferases contribute to shaping the pluripotent stem cell epigenome (Chapters 9-10). Using mouse ESCs null of DNA methylation, we determined DNA methylation regulates a large set of genes through action with H3K27me3. Furthermore, we determined shared and unique genomic targets of each DNA methyltransferase, including novel de novo methylation activity for Dnmt1 in vivo. In the human model system, we generated iPSCs from ICF Syndrome patient fibroblasts which carry double heterozygous mutations in DNMT3B. We found DNMT3B is involved in a wave of de novo methylation during the reprogramming process and has unique genomic targets.