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This book entitled “Cancer Stem Cell Markers and Related Network Path-ways” is about cancer stem cell (CSC) markers and the molecular network pathways. CSCs play an important role in the cancer drug resistance, metastasis and recurrence. Epithelial-mesenchymal transition (EMT) is closely related to CSC phenotype.This book covers various aspects of the molecular networks related to CSCs including the important phenotypic change such as EMT. Readers will discover the importance of the identification of CSC markers and EMT-related molecules in CSC network pathways.The CSC signaling pathways and EMT molecular network pathways attract researchers in the field to define the cancer therapeutic targets. Cancer environment is important in the acquisition of CSC phenotype in cells. The revealing of this CSC mystery is across 7 chapters. The topic of this book is particularly relevant to research in thefield of cancer and stem cells, as well as the network pathways. We hope that this book helps the readers to be interested in understanding why the CSC concept is important and attractive.

Perinatal and Developmental Epigenetics, Volume 32, a new volume in the Translational Epigenetics series, provides a thorough overview of epigenetics in the early developmental and perinatal stages, illuminating pathways for drug discovery and clinical advances. Here, over 25 international researchers examine recent steps forward in our understanding of epigenetic programming during perinatal and early development. The book opens with an in-depth introduction to known and newly discovered epigenetic marks and how they regulate various cellular processes. Later sections examine various prenatal and perinatal environmental experiences and their ability to derail the normal developmental trajectory via epigenetic reprogramming. Insights and suggestions for future research illuminate approaches for identifying individual disease susceptibility. Concluding chapters highlight preventative and targeted therapeutic pathways to improve quality of life into adulthood. - Examines disease onset stemming from epigenetic changes during the perinatal periods - Features contributions from international experts in the field, including basic biology, disease research and drug discovery - Offers intervention strategies to mitigate adverse developmental programming to improve health outcomes

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

This textbook will support graduate students with learning materials rich in the basic concepts of stem cell biology, in its most widespread and updated perspective. The chapters are conceived in a way for students to understand the meaning of pluripotency, the definition of embryonic stem cells and the formation of multicellular structures such as organoids together with the underlying principles of their epigenetic. This textbook also discusses adult stem cells and the potential use of these cells, in particular neural, mesenchymal, and several types of muscular cells, in biomedical research and clinical applications.This textbook represents a vital complement to the text on Essential Current Concepts of Stem Cell Biology, also published in the Learning Materials in Biosciences textbook series.

This multivolume reference work addresses the fact that the well being of humankind is predicated not only on individuals receiving adequate nutrition but also on their genetic makeup. The work includes more than 100 chapters organized in the following major sections: Introduction and Overview; Epigenetics of Organs and Diseases in Relation to Diet and Nutrition; Detailed Processes in Epigenetics of Diet and Nutrition; Modulating Epigenetics with Diet and Nutrition; and Practical Techniques. While it is well known that genes may encode proteins responsible for structural and dynamic components, there is an increasing body of evidence to suggest that nutrition itself may alter the way in which genes are expressed via the process of epigenetics. This is where chemically imposed alteration in the DNA sequence occurs or where the functional expression of DNA is modulated. This may include changes in DNA methylation, non-coding RNA, chromatin, histone acetylation or methylation, and genomic imprinting. Knowledge regarding the number of dietary components that impact on epigenetic processes is increasing almost daily. Marshalling all the information on the complex relationships between diet, nutrition, and epigenetic processes is somewhat difficult due to the wide myriad of material. It is for this reason that the present work has been compiled.

Five leaders in the field of mammalian preimplantation embryo development provide their own perspectives on key molecular and cellular processes that mediate lineage formation during the first week of life. The first cell-fate decision involves the formation of the pluripotent inner cell mass (ICM) and extraembryonic trophectoderm (TE). The second cell-fate choice encompasses the transformation of ICM into extraembryonic primitive endoderm (PE) and pluripotent epiblast. The processes, which occur during the period of preimplantation development, serve as the foundation for subsequent developmental events such as implantation, placentation, and gastrulation. The mechanisms that regulate them are complex and involve many different factors operating spatially and temporally over several days to modulate embryonic chromatin structure, impose cellular polarity, and direct distinct gene expression programs in the first cell lineages.

Central dogma'was presented by Dr. Francis Crick 60 years ago. The information of nucleotide sequences on DNAs is transcribed into RNAs by RNA polymerases. We learned the mechanisms of how transcription determines function of proteins and behaviour of cells and even how it brings appearances of organisms. This book is intended for scientists and medical researchers especially who are interested in the relationships between transcription and human diseases. This volume consists of an introductory chapter and 14 chapters, divided into 4 parts. Each chapter is written by experts in the basic scientific field. A collection of articles presented by active and laboratory-based investigators provides recent advances and progresses in the field of transcriptional regulation in mammalian cells.

Much research has focused on the basic cellular and molecular biological aspects of stem cells. Much of this research has been fueled by their potential for use in regenerative medicine applications, which has in turn spurred growing numbers of translational and clinical studies. However, more work is needed if the potential is to be realized for improvement of the lives and well-being of patients with numerous diseases and conditions. With a goal to accelerate advances by timely information exchange, this new book series'Cell Biology and Translational Medicine (CBTMED)'as part of SpringerNature's longstanding and very successful Advances in Experimental Medicine and Biology book series is launched. Emerging areas of regenerative medicine and translational aspects of stem cells will be covered in each volume. Outstanding researchers are recruited to highlight developments and remaining challenges in both the basic research and clinical arenas. This current book is the first volume of a continuing series.

This volume provides the reader with an overview of the diverse functions of the RUNX family of genes. As highlighted in the introduction and several of the 29 chapters, humans and other mammals have three RUNX genes that are known to play specific roles in blood, bone and neuronal development. However, their evolutionary history has recently been traced back to unicellular organisms and their involvement in many well-known signaling pathways (Wnt, TGFb, Notch, Hippo) is indicative of a more general function in cell biology. Their documented roles in cell fate decisions include control of proliferation, differentiation, survival, senescence and autophagy. The pleiotropic effects of RUNX in development are mirrored in cancer, where RUNX genes can function as oncogenes that collaborate strongly with Myc family oncogenes or as tumour suppressor genes. In the latter role, they display hallmarks of both ‘gatekeepers'that modulate p53 responses and ‘caretakers'that protect the genome from DNA damage. Several chapters focus on the importance of these genes in leukemia research, where RUNX1 and CBFB are frequently affected by chromosomal translocations that generate fusion oncoproteins, while recent studies suggest wider roles for RUNX modulation in solid cancers. Moreover, RUNX genes are intimately involved in the development and regulation of the immune system, while emerging evidence suggests a role in innate immunity to infectious agents, including HIV. At the biochemical level, the RUNX family can serve as activators or repressors of transcription and as stable mediators of epigenetic memory through mitosis. Not surprisingly, RUNX activity is controlled at multiple levels, this includes miRNAs and a plethora of post-translational modifications. Several chapters highlight the interplay between the three mammalian RUNX genes, where cross-talk and partial functional redundancies are evident. Finally, structural analysis of the RUNX/CBFB interaction has led to the development of small molecule inhibitors that provide exciting new tools to decipher the roles of RUNX in development and as targets for therapy. This volume provides a compendium and reference source that will be of broad interest to cancer researchers, developmental biologists and immunologists.

This book offers representative examples from fly and mouse models to illustrate the ongoing success of the synergistic, state-of-the-art strategy, focusing on the ways it enhances our understanding of sensory processing. The authors focus on sensory systems (vision, olfaction), which are particularly powerful models for probing the development, connectivity, and function of neural circuits, to answer this question: How do individual nerve cells functionally cooperate to guide behavioral responses? Two genetically tractable species, mice and flies, together significantly further our understanding of these processes. Current efforts focus on integrating knowledge gained from three interrelated fields of research: (1) understanding how the fates of different cell types are specified during development, (2) revealing the synaptic connections between identified cell types (“connectomics”) using high-resolution three-dimensional circuit anatomy, and (3) causal testing of how identified circuit elements contribute to visual perception and behavior.

This book presents epigenetics research as a new way of looking at genetics. Topics range from basic epigenetics mechanisms to development of cells and organisms and the biological basis of diseases. In addition the book focuses on immunology and the role of viruses in epigenetics. The last part of the book highlights proteins and peptides as epigenetic modulators.

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.

During vertebrate hematopoiesis many specialized cell types are formed with vastly different functions such as B cells, T cells, granulocytes, macrophages, erythrocytes and megakaryocytes. To tightly control the enormous proliferative potential of developing blood cells, an intricately balanced signaling and transcription network has evolved that ensures that the different cell types are formed at the right time and in the right numbers. Intricate regulatory mechanisms ensure that blood cells function properly and have a determined life span. Moreover, in the adaptive immune system, long-lived memory cells have evolved that ensure that when pathogens have been seen once they will never cause a problem again. In this book we will therefore make a journey from asking how more primitive organisms use the epigenetic regulatory machinery to balance growth with differentiation control towards digging deep into what controls the function of specialized cells of the human immune system. We will first discover that flies make blood but exist without blood vessels, why fish make blood cells in the kidney and which precise genetic circuitries are required for these developmental pathways. We will then learn the regulatory principles that drive the differentiation of mature blood cells from stem cells and what controls their function in mammals. In the process, we will find out what unites hematopoietic stem cells and endothelial cells. Finally, we will shed light on the molecular mechanisms that either alter hematopoietic cell differentiation or lead to the development of cells with impaired function.

This book will provide an overview of basic epigenetic phenomena; interaction between epigenetic and genetic factors; and the influence of epigenetic factors on inheritance. Epigenetic states may contribute to the penetrance of genetic polymorphisms or mutations and thereby modify inheritance patterns. This may result in non‐Mendelian inheritance of genetic traits such as observed in common human disease. The relationship between epigenetics and genetics, however, has not been comprehensively summarized yet. The topic is being more and more appreciated lately due to considerable advances in genomic and epigenomic approaches to study the origins of human disease. The editors will focus not only on describing epigenetic characteristics, mechanisms and results, but also on how considerations of epigenetics can alter interpretation and analysis of risks for complex traits. This book will be a resource for those who have been working in human genetics or analysis of human genetic data and are studying the impact of epigenetics on inheritance. An overview will be given of the impacts of inter‐individual variation in epigenetic states from major changes (errors in genomic imprinting) that cause congenital developmental defects to subtle changes and their impact on complex traits. The editors will discuss the relationship between epigenetic changes and genetic changes in human disease. Several chapters will also focus on statistical analysis of epigenetics effects, either in human disease genetic studies, or in population genetics. ​

Genetically-engineered mouse models for cancer research have become invaluable tools for studying cancer biology and evaluating novel therapeutic approaches. This volume focuses on state-of-the-art methods for generating, analyzing and validating such models for studying aspects of human cancer biology. Additionally, these models are emerging as important pre-clinical systems in which to test cancer prevention and therapeutic strategies in order to select compounds for testing in clinical trials.

The mouse is a perfect model organism to study mammalian, and thus indirectly also human, embryology. Most scientific achievements that have had an important impact on the understanding of basic mechanisms governing embryo development in humans, originated from mouse embryology. Stem cell research, which now offers the promise of regenerative medicine, began with the isolation and culture of mouse embryonic stem cells by Martin Evans (who received the Nobel Prize in medicine in 2007 for this achievement) and Matthew Kaufman. This book provides an overview of mouse development, spanning from oocytes before fertilization to the state-of-the-art description of embryonic and adult stem cells. The chapters, written by the leading specialists in the field, deal with the most recent discoveries in this extremely fast-developing area of research.

The central question of this book is whether or not particular cell entities of human origin ought to be considered human beings. The answer is crucial for making moral decisions for or against research and experimentation. Experts in the field discuss the production of embryonic-like pluripotent stem cells by altered nuclear transfer, parthenogenesis and reprogramming of adult somatic cells. They thoroughly analyse the biological and moral status of different cell entities, such as human stem cells, embryos and human-animal hybrid embryos, and make a decisive step towards establishing final criteria for what constitutes a human being. The topic is challenging in nature and of broad interest to all those concerned with current bioethical thought on embryonic human life and its implications for society.

Epigenetics has emerged recently as an important area of molecular biological studies. Epigenetic modifications lead to potentially heritable but reversible alterations in the expression of genes that determine cell fate. Epigenetic misregulation is thus often linked to degenerative diseases, cancer and neuronal disorders. Recent biomedical interest in this regulatory system stems from the fact that epigenetic, in contrast to genetic, alterations are in principle amenable to pharmacological intervention. A few epigenetically active drugs, for example histone deacetylase inhibitors (HDACi) and DNA methyltransferase (DNMT) inhibitors, have been approved by FDA for treatment of cancers such as CTCL, MDS, and AML. This volume explores the scientific background for clinical applications of epigenetically active drugs. Included are descriptions of epigenetic controls over gene expression, the post-transcriptional silencing of genes by RNA interference (RNAi) and microRNAs, as well as new findings from stem cell research which are relevant to pharmacological applications.

Epigenetics is a rapidly expanding field in medical and biological research which concerns heritable traits that are not attributable to changes in the DNA sequence. Epigenetic mechanisms play key roles in many biological processes, and it has become clear that their disruption can gives rise to diverse pathologies in humans. Edited by preeminent experts, Sophie Rousseaux and Saadi Khochbin, this volume in the ‘Epigenetics and Human Health'series discusses the role of epigenetics in human reproduction

Leading experts provide timely and comprehensive information on methods for conditional mutagenesis in the mouse (part 1) and their application to model human physiology and pathophysiology (part 2). It illustrates how sophisticated genetic manipulations of the mouse genome are employed to model human diseases and to identify underlying molecular mechanisms. Finally the book considers the development of new drugs to treat them.

The completion of the human genome and technological advances developed by the Human Genome Project have dramatically changed our understanding of the mechanisms underlying the development and differentiation of male germ cells, and our ability to investigate such mechanisms. This book is a timely document of advances made in the field of male gonad and germ cell research in the postgenomic era.The coverage includes the role of Y chromosome genes in male reproduction, gene expression in spermatogonial stem cells and male germ cells, and the regulation of germ cell genes in reproduction and in germ cell tumors.

Our goal has been aimed to do a molecular examination of these homeobox family members, which are differentially expressed during the early embryonic development and periimplantation. With this purpose, we would like to enrich our group of knowledge in the molecular reproduction, which helps to understand these natural or abnormal developmental phenomena, frequently caused by the pressure of the oocyte or the embryonic surroundings (Gandolfi et al. 2005). Because such stress conditions have been seen to drive placental defects, postnatal oversize or overweight (LOS), as well as organs failures in the offspring, still as adult diseases (Young et al. 1998). On this hand a lot of effects in the molecular biology could be related with these developmental mechanisms involved in the mammalian reproduction (McEvoy et al. 2001, 2003, Farin et al. 2006, Laurincik et al. 2003, Lonergan et al. 2003a, b, 2004, 2006, Wrenzycki et al. 2005b, Ecker et al. 2004). Many studies have been abundantly realized in the Homeobox mRNA and protein expression around implantation, as well as during primary differentiation events in the early mammalian development, also after blastocyst expansion, gastrulation, primitive streak formation, embryonic disk proliferation, organogenesis and limbogenesis (Beck et al. 1995, 1999, 2000, Charité et al. 1998, Chawengsaksophak et al. 1996, 1997, 2004, Deschamps et al. 1999, Manzanares and Krumlauf 2000). All these works have been focussed to determine the expression of Hox genes combination as well known as the Hox-code. This network appears to be very important in the spatial and temporal co- linearity during the early body patterning (Deschamps et al. 1999). Still, a lot of works have been directed on the mRNA and protein expression of the caudal members (Cdx) transcription factors as regulators of the Hox-gene expression among other genes, recently well reviewed by Deschamps and van Nes (2005) and Grier et al. (2005). The A-P patterning and the body-tissue identity of the mammalian embryo, as by others living beings, are directed by the interaction of the nuclear transcription factors as the homeodomain related proteins activity (van Nes et al. 2006, Pilon et al. 2006). The stress by surroundings appears to be highly related to placental and body-tissue development defects (Hall et al. 2005).

Rheumatoid Arthritis (RA) represents a complex disease where the inheritable component has been estimated to be up to 60%. This PIR volume deals with the genetic basis and regulation of rheumatic diseases. The first part of the book describes genetic studies on rheumatic diseases. The second part deals with the shared heredity of rheumatic diseases, e.g., RA, lupus and ankylosing spondylitis. The third part of the volume describes tools for analysing genetic complexity, ranging from animal models to new molecular tools. The volume is essential reading for researchers and clinicians from rheumatology, inflammation research, immunology, and cell and molecular biology.

Disorders that affect tissue differentiation, organogenesis, and morphogenesis constitute a significant proportion of human hereditary diseases. Until very recently, however, their genetic causes and pathogenesis have been unknown. Now, with the elucidation of the molecular pathways that govern developmental processes and with advances in gene identification, the genetic bases of an increasing number of human disorders of development are being discovered and the links between genotype and phenotype established. This extraordinary volume is the first to present in-depth analyses of the human syndromes of abnormal morphogenesis for which the responsible genes have been identified. Following a series of introductory chapters on the general principles of developmental biology, developmental genetics, and the development of individual tissues or organ systems, more than one hundred clinical genetic disorders are considered. The clinical chapters are organized into sections by defined developmental pathways or gene families, and each section is preceded by a general overview. For each disorder the authors cover the disease-causing genes, the role of these genes in development as elucidated in model organisms, the human mutations that have been identified, and the developmental pathogenesis of the condition. Clinical descriptions, along with discussions of therapy and counseling, are provided. This book will be an invaluable resource for physicians, dentists, and other health professionals and for basic scientists interested in developmental processes and genetic perturbations that affect them. It is authoritative, clearly written, consistently organized, and attractively illustrated in color.