Stem Cell Proliferation and Differentiation


Book Description

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




Transcriptional and Translational Regulation of Stem Cells


Book Description

This volume describes the latest findings on transcriptional and translational regulation of stem cells. Both transcriptional activators and repressors have been shown to be crucial for the maintenance of the stem cell state. A key element of stem cell maintenance is repression of differentiation factors or developmental genes – achieved transcriptionally, epigenetically by the Polycomb complex, and post-transcriptionally by RNA-binding proteins and microRNAs. This volume takes two approaches to this topic – (1) illustrating the general principles outlined above through a series of different stem cell examples – embryonic, iPS and adult stem cells, and (2) describing several molecular families that have been shown to have roles in regulation of multiple stem cell populations.




Regulation of Stem Cell Proliferation and Differentiation by Drosophila Sox21a and Sox100B in the Adult Intestine


Book Description

Proper maintenance of tissue homeostasis is essential for the organism's architecture and function. In many tissues, homeostasis is maintained by resident stem cells that precisely adapt their proliferation and differentiation to tissue demands, especially in response to stress and injury. However, the underlying mechanisms are largely unclear. Importantly, mis-regulation of either stem cell proliferation or differentiation is associated with tissue degeneration and tumor formation. Therefore, understanding the basic mechanisms by which stem cell activities are precisely controlled is a critical step towards understanding the physiological causes of many diseases. The Drosophila midgut epithelium is actively maintained by intestinal stem cells (ISCs) and has proven to be a valuable model to study regulation of stem cell activities both at homeostasis and in response to stress. Here I focus on two Sox family transcription factors, Sox21a and Sox100B, and investigate their expression patterns and functions in the adult Drosophila intestine. In the first part of this dissertation, I present data showing that Sox21a acts as a critical regulator of adult ISC proliferation. I found that ISC-specific Sox21a expression is required for basal and stress-induced ISC proliferation. Interestingly, Sox21a expression is increased upon stress exposure to promote ISC proliferation. Furthermore, I showed that Sox21a induction integrates signal inputs from multiple stress signaling pathways to regulate injury-induced ISC proliferation. The mechanism by which ISC/EB-specific Sox21a expression pattern is generated is not clear. I screened the Sox21a locus and found that the 1st intron of Sox21a is sufficient to generate this pattern and thus I generated an in vivo reporter. In the second part of my dissertation, I present data showing that Sox100B is required for Sox21a reporter expression, as well as endogenous Sox21a expression, indicating that Sox21a is a target gene of Sox100B. I found that Sox100B is required for proper ISC differentiation, highlighting a role of this Sox regulatory network in the process of ISC differentiation. Altogether, my work uncovered a Sox transcriptional network which interacts with stress-sensing signaling pathways, precisely regulating ISC proliferation and differentiation at homeostasis and in response to stress to maintain tissue homeostasis. My findings may inform studies of other stem cell populations,including in humans.




Stem Cell Regulators


Book Description

Factors operating in pluripotent cells -- Molecular mediators of Mesenchymal Stem Cell (MSC) -- Insulin and germline proliferation in Caenorhabditis -- Generation of mature ß-cells from embryonic stem cells: What are we missing? -- Activation and regulation of reserve liver progenitor cells -- Adult cardiac-derived stem cells: differentiation and survival regulators -- TGF-Beta1 regulates differentiation of bone marrow mesenchymal stem cells -- Maternal intake of folic acid and neural crest stem cells -- Modulation of the generation of dopaminergic neurons from human neural stem cells by Bcl-XL. Mechanisms of action -- Glucocorticoid hedgehog agonists in neurogenesis -- Effect of progesterone on human mesenchymal stem cells -- Regulation of muscle stem cell activation -- the role of growth factors and extracellular matrix -- Thymosins and muscle regeneration -- Micro RNAs and mesenchymal stem cells -- MicroRNA and vascular smooth muscle cells -- Transforming growth factor beta superfamily in mouse embryonic stem cell self-renewal -- The biology of HIFa proteins in cell differentiation and disease -- Regulatory role of Klf5 in early mouse development and in embryonic stem cells -- Bam and Bgcn in Drosophila germ line stem cell differentiation -- The effects of mechanical loading on mesenchymal stem cell differentiation and matrix production.




Regulatory Networks in Stem Cells


Book Description

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 Cell Epigenetics


Book Description

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




Transcriptional Regulation of Intestinal Stem Cells and Differentiation


Book Description

The intestinal epithelium is one of the most rapidly self-renewing tissues in the body and thus the ideal tissue for studying somatic progenitor and stem cell biology. The intestinal epithelium is composed of a single layer of cells that contains four major differentiated cell types as well as intestinal stem cells (ISCs) and progenitor cells that replenish differentiated cells throughout life. However, the molecular mechanisms that govern the self-renewal and differentiation of ISCs are only partially understood. Previously, one of the terminally differentiated epithelial cell types, the Paneth cells, were proposed to be the ISC "niche." However, subsequent studies have found ablation of Paneth cells in mice showed no effect on either stem cell maintenance or proliferation. I have analyzed the poorly understood mesenchymal contribution to epithelial stem cell maintenance and homeostasis by generating Foxl1-hDTR transgenic mice, in which the human diphtheria toxin receptor (hDTR ) is placed under the control of the Foxl1 promoter. Foxl1 is exclusively expressed in the subepithelial mesenchyme of the adult gastrointestinal tract. Ablation of Foxl1+ mesenchymal cells resulted in severe weight loss and disruption of epithelial architecture and a dramatic reduction in proliferation of both epithelial stem and transit-amplifying progenitor cells. I found that these effects are caused by the loss of activated Wnt/[beta]-catenin signaling signaling in the epithelium. Taken together, I have identified a novel mesenchymal ISC niche that supports both proliferation and maintenance of stem cells possibly through providing important Wnt ligands.




Stem Cells in Reproductive Medicine


Book Description

Stem cell science has the potential to impact human reproductive medicine significantly - cutting edge technologies allow the production and regeneration of viable gametes from human stem cells offering potential to preciously infertile patients. Written by leading experts in the field Stem Cells in Reproductive Medicine brings together chapters on the genetics and epigenetics of both the male and female gametes as well as advice on the production and regeneration of gene cells in men and women, trophoblasts and endometrium from human embryonic and adult stem cells. Although focussing mainly on the practical elements of the use of stem cells in reproductive medicine, the book also contains a section on new developments in stem cell research. The book is essential reading for reproductive medicine clinicians, gynecologists and embryologists who want to keep abreast of practical developments in this rapidly developing field.




Stem Cell Biology and Regenerative Medicine, Second edition


Book Description

The study of stem cell biology is under intensive investigation. Because stem cells have the unique capability to self-renew and differentiate into one or several cell types, they play a critical role in development, tissue homeostasis and regeneration. Stem cells also constitute promising cell candidates for cell and gene therapy. The aim of this book is to provide readers and researchers with timely and accurate knowledge on stem cell biology and regenerative medicine. This book will cover many topics in the field and is based on conferences given by recognized scientists involved in the international master course on stem cell biology at Sorbonne Université in Paris.