Chemical and Functional Genomic Approaches to Stem Cell Biology and Regenerative Medicine


Book Description

Scientists believe that stem cells have the potential to revolutionize the treatment of numerous diseases and conditions. This guide covers recent advances in technologies and their applications in stem cell biology, addressing the use of both embryonic and adult stem cells and discussing diverse technologies, including genome-wide expression analysis, informatics, chemical genomics, and more. Applications covered encompass self-renewal, differentiation, reprogramming, and regeneration in model organisms. This is a premier reference for practicing professionals involved in stem cell research and students.




Functional Genomics Study to Understand the Role of Serotonin in Mouse Embryonic Stem Cells


Book Description

Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter that is synthesized from the amino acid L-tryptophan and is reported to localize in mitochondria of embryonic stem cells. Even before its role as a neurotransmitter in mature brain was discovered, 5-HT has been shown to play an important role in regulating brain development. However, there is a lack of knowledge about the downstream target genes regulated by serotonin in embryonic stem (ES) cells. Towards this end, our study helps in understanding transcriptional regulatory mechanisms of 5-HT responsive genes in ES cells. By combining the gene expression data with motif prediction algorithms, literature validation and comparison with public domain data, gene targets specific to endogenous or exogenous 5-HT in ES cells were identified. By performing one-way ANOVA, and volcano plots using GeneSpring software, we identified 44 5-HT induced and 29 5-HT suppressed genes, likely to be transcriptionally regulated by 4 & 2 TFs respectively. Motif enrichment analysis on these target genes using MotifScanner revealed that the transcription factor TFAP2A plays a key role in regulating the expression of 5-HT responsive genes. Furthermore, by comparing our dataset with published expression profiles of ES cells, we observed a number of 5-HT responsive target genes showing enrichment in ES cells. Genes such as Nanog, Slc38a5, Hoxb1 and Eif2s1 from this analysis have been observed to be components of 'stemness' phenotypes reported in literature. Functional annotation of the 5-HT responsive genes identified gene ontologies such as regulation of translation in response to stress and energy derivation by oxidation, suggesting a regulatory role for 5-HT in mitochondrial functions of ES cells. Additionally, enrichment of other biological process terms such as development of various parts of nervous system, cell adhesion, and apoptosis suggests that 5-HT target genes may play an important role in ES cell differentiation. Our study implemented a new combinatorial approach for identifying gene regulatory mechanisms involved in 5-HT responsive genes and proposed potential mediatory role for serotonin in ES cell differentiation and growth. Thus, this study provides potential 5-HT target genes in ES cells for biological validation.




Next Steps for Functional Genomics


Book Description

One of the holy grails in biology is the ability to predict functional characteristics from an organism's genetic sequence. Despite decades of research since the first sequencing of an organism in 1995, scientists still do not understand exactly how the information in genes is converted into an organism's phenotype, its physical characteristics. Functional genomics attempts to make use of the vast wealth of data from "-omics" screens and projects to describe gene and protein functions and interactions. A February 2020 workshop was held to determine research needs to advance the field of functional genomics over the next 10-20 years. Speakers and participants discussed goals, strategies, and technical needs to allow functional genomics to contribute to the advancement of basic knowledge and its applications that would benefit society. This publication summarizes the presentations and discussions from the workshop.










The Physiological Genomics of the Critically Ill Mouse


Book Description

The physiological genomics of the cardiovascular system studies the relationship between gene and physiological (dys)function. It is a rapidly developing area of research and distinguishes itself from other areas of molecular medicine by its highly integrative nature. In this multi disciplinarian area of the physiological sciences, there is interaction between gene structure and physiological cardiovascular function as well as interactions between the different organs and their physiological compartments. The mouse has played a central role in the study of genomics due to the detailed knowledge of the mouse genome and the wide availability of genetically modified mice. In the past, the mouse had mainly been used in the area of immunology and molecular biology, and physiological interest in the mouse was scarce. As more insight has come into the structural genomics of the mouse, however, it has become increasingly important to understand the relation between gene and physiological function. With this in mind we have been organizing the Amsterdam Mouse Symposia to bring together different disciplines interested in the molecular basis of cardiovascular function (see J. of Clinical and Exp. Pharmacology and rd Physiology (2002) 29:A69-AI02 for the proceedings of the 3 Amsterdam Mouse Symposium and Basic Research in Cardiology (2000) 95:492-535 for nd the proceedings of the 2 symposium).




Guide to Techniques in Mouse Development


Book Description

17 years have passed since the first edition of the Guide to Techniques in Mouse Development (volume 225) was published. During this time development of technology used to investigate mouse development has not stood still, with enormous advances occuring in genomics, transgenic and ES cell methodology, and reprogramming, culminating with development of iPS cells. At both the cellular and molecular levels, a great many technological advances have been made that permit investigators to probe ever more deeply into all aspects of mouse development. This completely new version of the Guide has been split into two parts, both highlighting the techonological advances used to study mouse development.




Gene Targeting and Embryonic Stem Cells


Book Description

Gene Targeting and Embryonic Stem Cells is a practical guide designed for the rapidly growing number of researchers who are moving into this field. Provides details on how to culture, transfect and differentiate established cell lines, and how to isolate new cell lines. Gene targeting experiments are described for a number of cell types, including ungulate fetal fibroblasts, murine ES cells, human embryonal carinoma cells and human ES cells, and include protocols for gene-targeting vectors, DNA transfection and RNA interference. The recent isolation of human embryonic stem cells and the potential of these cells for therapeutic applications has generated an entirely new methodology. Similarly, gene targeting methodology has recently been extended to nuclear donor cells in ungulate species. This volume will be invaluable for both new and established researchers in the field of human embryonic stem cells, and to biotech companies engaged in the production of transgenic proteins in livestock, xenotransplantation and the development of animal models.




The Physics of Living Systems


Book Description

In this book, physics in its many aspects (thermodynamics, mechanics, electricity, fluid dynamics) is the guiding light on a fascinating journey through biological systems, providing ideas, examples and stimulating reflections for undergraduate physics, chemistry and life-science students, as well as for anyone interested in the frontiers between physics and biology. Rather than introducing a lot of new information, it encourages young students to use their recently acquired knowledge to start seeing the physics behind the biology. As an undergraduate textbook in introductory biophysics, it includes the necessary background and tools, including exercises and appendices, to form a progressive course. In this case, the chapters can be used in the order proposed, possibly split between two semesters. The book is also an absorbing read for researchers in the life sciences who wish to refresh or go deeper into the physics concepts gleaned in their early years of scientific training. Less physics-oriented readers might want to skip the first chapter, as well as all the "gray boxes" containing the more formal developments, and create their own á-la-carte menu of chapters.