Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development


Book Description

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.




Epigenetic Regulation of Lymphocyte Development


Book Description

The studies described in this volume serve as a starting point to familiarize one self with the multifarious differences in epigenetic designs that orchestrate the progression of developing blood cells. They also may serve as a general paradigm for the mechanisms that underpin the control of eukaryotic gene expression.




Epigenetic Gene Expression and Regulation


Book Description

Epigenetic Gene Expression and Regulation reviews current knowledge on the heritable molecular mechanisms that regulate gene expression, contribute to disease susceptibility, and point to potential treatment in future therapies. The book shows how these heritable mechanisms allow individual cells to establish stable and unique patterns of gene expression that can be passed through cell divisions without DNA mutations, thereby establishing how different heritable patterns of gene regulation control cell differentiation and organogenesis, resulting in a distinct human organism with a variety of differing cellular functions and tissues. The work begins with basic biology, encompasses methods, cellular and tissue organization, topical issues in epigenetic evolution and environmental epigenesis, and lastly clinical disease discovery and treatment. Each highly illustrated chapter is organized to briefly summarize current research, provide appropriate pedagogical guidance, pertinent methods, relevant model organisms, and clinical examples. Reviews current knowledge on the heritable molecular mechanisms that regulate gene expression, contribute to disease susceptibility, and point to potential treatment in future therapies Helps readers understand how epigenetic marks are targeted, and to what extent transgenerational epigenetic changes are instilled and possibly passed onto offspring Chapters are replete with clinical examples to empower the basic biology with translational significance Offers more than 100 illustrations to distill key concepts and decipher complex science




Epigenetic Mechanisms in Cellular Reprogramming


Book Description

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.




Epigenetics: Development and Disease


Book Description

Epigenetics fine-tunes the life processes dictated by DNA sequences, but also kick-starts pathophysiological processes including diabetes, AIDS and cancer. This volume tracks the latest research on epigenetics, including work on new-generation therapeutics.




Epigenetics and Regeneration


Book Description

Epigenetics and Regeneration compiles the first foundational reference on epigenetic mechanisms governing tissue development, repair, homeostasis, and regeneration, as well as pathways to employ these mechanisms in clinical practice and translational science. In this book, life science researchers, clinicians, and students will discover an interdisciplinary resource bringing together common themes in the field, background overviews, research methods, recent advances, and opportunities for drug discovery. Throughout this volume, special attention is paid to pre-clinical and first clinical studies aimed at increasing the regenerative potential of damaged tissues by epigenetic drugs, as well as innovative, discipline spanning strategies to enhance cell reprogramming. As an all-inclusive, evidence-based volume, Epigenetics and Regeneration will stimulate discussion and boost new research in this fascinating and impactful area of translational epigenetics. Provides a foundational overview of epigenetics in regenerative medicine Examines epigenetic components of tissue regeneration for a variety of organ systems and tissue types, as well as current attempts to employ these mechanisms in clinical practice Offers researchers, students, clinicians, and pharmacologists the tools they need to enhance tissue development, repair, homeostasis, and regeneration and explore new epigenetic therapeutic pathways Features chapter contributions from leading international researchers and clinicians in the fields of epigenetics and regenerative medicine




Epigenetics and Reproductive Health


Book Description

Epigenetics and Reproductive Health, a new volume in the Translational Epigenetics series, provides a thorough overview and discussion of epigenetics in reproduction and implications for reproductive medicine. Twenty international researchers discuss epigenetic mechanisms operating during the formation of male and female gametes, fertilization and subsequent embryo and placental development, particularly in mammals and transgenerational epigenetic inheritance. This volume also addresses aberrant epigenetic changes influencing male and female infertility, pregnancy related disorders, and those potentially linked to therapeutic manipulations and assisted reproductive technologies. Emphasis is placed on identifying biomarkers for early detection of aberrant epigenetic mechanisms. Later chapters examine the possibility of correcting these epigenetic dysfunctions, as well as current challenges and next steps in research, enabling new translational discoveries and efforts towards developing therapeutics. Thoroughly examines the influence of aberrant epigenetics during gametogenesis and embryogenesis, affecting parents, gametes and embryos, offspring and future generations Explores health outcomes for reproductive senescence, endocrine disruption, testicular cancer, prostrate cancer, breast cancer, ovarian, cancer, endometrial cancer and cervical cancers Features chapter contributions from international researchers in the field




Transcriptional and Epigenetic Mechanisms of the First Cell Fate Decision and Reprogramming


Book Description

The placenta is a transient but vital organ mediating a myriad of interactions between maternal and embryonic tissues. The cells in the trophectoderm (TE) lineage are responsible for proper implantation, placentation, and immunological functions of the placenta. However, our understanding of molecular mechanisms underlying placentation and TE development is still rudimentary. Deciphering the mechanisms by which key TE-specific transcription factors (TFs) control the first cell fate decision, as well as the maintenance and differentiation of TE, is a prerequisite for understanding early embryonic development and ultimately improving healthy pregnancy. First, using a combination of functional genomics, bioinformatics, and mouse genetics, I revealed that Arid3a is a critical regulator for controlling the first cell fate decision and placental development. Ectopically expressed Arid3a induces TE-like gene expression programs in embryonic stem (ES) cells. Moreover, Arid3a is not only essential for maintaining self-renewing TS cells, but also for promoting further differentiation of trophoblastic lineages. Consistently, Arid3a-/- mice suffer from severely impaired post-implantation development, resulting in early embryonic lethality. I further showed that Arid3a directly activates TE-specific genes while repressing pluripotency genes by recruiting HDAC1. Second, I studied the mechanisms underlying TF-mediated conversion of ES to trophoblast stem (TS)-like cells. Upon overexpression of TS cell-specific TFs, Cdx2, Arid3a, and Gata3 (CAG factors) in ES cells, I performed time–course profiling of chromatin accessibility, transcriptomes, and occupancy of these reprogramming factors during reprogramming. Using an integrative analysis, I discovered that CAG factors orchestrate the conversion via a sequential two-step regulation in a timely, ordered manner, with repression of pluripotency genes by decommissioning active enhancers, followed by activation of TS cell-specific genes as pioneer factors that can access closed chromatin. Taken together, my studies unveiled that Arid3a functions as a pivotal regulator of TE and placental development by regulating the commitment to the first cell fate, as well as by executing TE lineage differentiation. I advanced our understanding of the mechanisms underlying TF-mediated reprogramming of ES to TS-like cells, in particular Arid3a-mediated transcriptional and epigenetic regulation. Thus, my studies will be beneficial for enhancing clinical applications such as disease modeling, drug screening, and regenerative therapies.




Epigenetic Contributions in Autoimmune Disease


Book Description

This volume focuses on the relevance of epigenetic mechanisms in autoimmune disease. It provides new directions for future research in autoimmune disease.




Epigenetic Regulation of Lymphocyte Development


Book Description

The studies described in this volume serve as a starting point to familiarize one self with the multifarious differences in epigenetic designs that orchestrate the progression of developing blood cells. They also may serve as a general paradigm for the mechanisms that underpin the control of eukaryotic gene expression.