Transposable Elements and the Regulatory Logic of Hematopoietic Differentiation PDF Download
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Author: Mohamad Ali Najia
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
The temporal regulation of gene expression by transcription factors, chromatin modifiers and cis-regulatory elements is central to establish cellular identity and function. Understanding this regulatory logic is critical for deriving select cell types in vitro for translational applications. The human hematopoietic system has long been a model system and an important source for adoptive cell therapies, yet, our understanding of the regulatory mechanisms that elicit commitment toward distinct hematopoietic lineages is continuously evolving. In this thesis, I describe several studies on transposable elements (TEs) as natural and engineered sources of regulatory innovation that contribute to, and aid in the investigation of, dynamic cellular processes. Toward this end, I built comprehensive genome-wide enhancer-gene maps spanning the human hematopoietic system and identified that TEs in the human genome contribute to the transcriptional networks regulating lymphoid cells. De-repression of TEs in hematopoietic stem cells, enacted via modulation of TE chromatin silencing machinery, facilitates the development of natural killer (NK) cells during lymphoid differentiation. Specifically, knockout of the H3K9 methyltransferase EHMT1 or transcriptional co-repressor TRIM28 induced NK-fated progenitors that ultimately generated NK cells with diverse effector properties. We further leveraged TEs by repurposing the packaging function of the MLV gag polyprotein to create a non-destructive reporter of the transcriptional states of living cells, enabling the measurement of dynamic transcriptional processes. Through engineering and scientific inquiry, I established the utility of TEs as synthetic biology tools, furthering our understanding of hematopoietic lineage decisions and highlighting that modulation of TEs can be enabling for hematopoietic cell engineering.
Author: Mohamad Ali Najia
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
The temporal regulation of gene expression by transcription factors, chromatin modifiers and cis-regulatory elements is central to establish cellular identity and function. Understanding this regulatory logic is critical for deriving select cell types in vitro for translational applications. The human hematopoietic system has long been a model system and an important source for adoptive cell therapies, yet, our understanding of the regulatory mechanisms that elicit commitment toward distinct hematopoietic lineages is continuously evolving. In this thesis, I describe several studies on transposable elements (TEs) as natural and engineered sources of regulatory innovation that contribute to, and aid in the investigation of, dynamic cellular processes. Toward this end, I built comprehensive genome-wide enhancer-gene maps spanning the human hematopoietic system and identified that TEs in the human genome contribute to the transcriptional networks regulating lymphoid cells. De-repression of TEs in hematopoietic stem cells, enacted via modulation of TE chromatin silencing machinery, facilitates the development of natural killer (NK) cells during lymphoid differentiation. Specifically, knockout of the H3K9 methyltransferase EHMT1 or transcriptional co-repressor TRIM28 induced NK-fated progenitors that ultimately generated NK cells with diverse effector properties. We further leveraged TEs by repurposing the packaging function of the MLV gag polyprotein to create a non-destructive reporter of the transcriptional states of living cells, enabling the measurement of dynamic transcriptional processes. Through engineering and scientific inquiry, I established the utility of TEs as synthetic biology tools, furthering our understanding of hematopoietic lineage decisions and highlighting that modulation of TEs can be enabling for hematopoietic cell engineering.
Author: Renato Paro
Publisher: Springer Nature
ISBN: 3030686701
Category : Science
Languages : en
Pages : 215
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Book Description
This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease
Author: Eric H. Davidson
Publisher: Elsevier
ISBN: 0080525598
Category : Science
Languages : en
Pages : 274
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Book Description
The interaction between biology and evolution has been the subject of great interest in recent years. Because evolution is such a highly debated topic, a biologically oriented discussion will appeal not only to scientists and biologists but also to the interested lay person. This topic will always be a subject of controversy and therefore any breaking information regarding it is of great interest.The author is a recognized expert in the field of developmental biology and has been instrumental in elucidating the relationship between biology and evolution. The study of evolution is of interest to many different kinds of people and Genomic Regulatory Systems: In Development and Evolution is written at a level that is very easy to read and understand even for the nonscientist. * Contents Include* Regulatory Hardwiring: A Brief Overview of the Genomic Control Apparatus and Its Causal Role in Development and Evolution * Inside the Cis-Regulatory Module: Control Logic and How the Regulatory Environment Is Transduced into Spatial Patterns of Gene Expression* Regulation of Direct Cell-Type Specification in Early Development* The Secret of the Bilaterians: Abstract Regulatory Design in Building Adult Body Parts* Changes That Make New Forms: Gene Regulatory Systems and the Evolution of Body Plans
Author: Mauro Giacca
Publisher: Springer Science & Business Media
ISBN: 8847016436
Category : Medical
Languages : en
Pages : 318
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Book Description
I entered the gene therapy field in the mid-1990s, being fascinated by the immense potential of genes as drugs for the treatment of human disease. Since then, I have experienced the ups and downs of this discipline, and tried to contribute with my work and that of my laboratory to the development of innovative approaches to the treatment of cardiovascular disorders. During these years, I have had several opp- tunities to speak on gene therapy at lectures and academic lessons, and have often noticed that the field is very attractive to scientists of all disciplines. However, as yet no comprehensive book on the subject has been published. Indeed, most books in the field are either a collection of gene transfer laboratory protocols or deal with the subject in a rather superficial manner. Hence the idea to write a gene therapy textbook that is broad and comprehensive, but at the same time provides sufficient molecular and clinical detail to be of interest to students, professors, and specialists in the various disciplines that contribute to gene therapy. I have tried to keep the language plain and, whenever possible, non-technical. Since the book is intended to be a textbook in the field of gene therapy in both the basic science and clinical areas, whenever technical descriptions are required, they are provided.
Author:
Publisher:
ISBN:
Category : Genetics
Languages : en
Pages : 634
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Book Description
Author: Krishnarao Appasani
Publisher: Cambridge University Press
ISBN: 9780521118552
Category : Science
Languages : en
Pages : 580
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Book Description
MicroRNAs (miRNAs) are RNA molecules, conserved by evolution, that regulate gene expressions and their recent discovery is revolutionising both basic biomedical research and drug discovery. Expression levels of MiRNAs have been found to vary between tissues and with developmental stages and hence evaluation of the global expression of miRNAs potentially provides opportunities to identify regulatory points for many different biological processes. This wide-ranging reference work, written by leading experts from both academia and industry, will be an invaluable resource for all those wishing to use miRNA techniques in their own research, from graduate students, post-docs and researchers in academia to those working in R&D in biotechnology and pharmaceutical companies who need to understand this emerging technology. From the discovery of miRNAs and their functions to their detection and role in disease biology, this volume uniquely integrates the basic science with industry application towards drug validation, diagnostic and therapeutic development. Forewords by: Sidney Altman, Yale University, Winner of the Nobel Prize in Chemistry, 1989 and Victor R. Ambros, Dartmouth Medical School, Co-discoverer of MicroRNAs
Author: Sam Thiagalingam
Publisher: Cambridge University Press
ISBN: 0521493390
Category : Mathematics
Languages : en
Pages : 597
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Book Description
An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.
Author: Isil Aksan Kurnaz
Publisher: CRC Press
ISBN: 1482260905
Category : Medical
Languages : en
Pages : 334
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Book Description
Although designed for undergraduates with an interest in molecular biology, biotechnology, and bioengineering, this book-Techniques in Genetic Engineering-IS NOT: a laboratory manual; nor is it a textbook on molecular biology or biochemistry. There is some basic information in the appendices about core concepts such as DNA, RNA, protein, genes, and
Author: Vincenzo E. A. Russo
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 716
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Book Description
Many inheritable changes in gene function are not explained by changes in the DNA sequence. Such epigenetic mechanisms are known to influence gene function in most complex organisms and include effects such as transposon function, chromosome imprinting, yeast mating type switching and telomeric silencing. In recent years, epigenetic effects have become a major focus of research activity. This monograph, edited by three well-known biologists from different specialties, is the first to review and synthesize what is known about these effects across all species, particularly from a molecular perspective, and will be of interest to everyone in the fields of molecular biology and genetics.
Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309452880
Category : Medical
Languages : en
Pages : 329
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Book Description
Genome editing is a powerful new tool for making precise alterations to an organism's genetic material. Recent scientific advances have made genome editing more efficient, precise, and flexible than ever before. These advances have spurred an explosion of interest from around the globe in the possible ways in which genome editing can improve human health. The speed at which these technologies are being developed and applied has led many policymakers and stakeholders to express concern about whether appropriate systems are in place to govern these technologies and how and when the public should be engaged in these decisions. Human Genome Editing considers important questions about the human application of genome editing including: balancing potential benefits with unintended risks, governing the use of genome editing, incorporating societal values into clinical applications and policy decisions, and respecting the inevitable differences across nations and cultures that will shape how and whether to use these new technologies. This report proposes criteria for heritable germline editing, provides conclusions on the crucial need for public education and engagement, and presents 7 general principles for the governance of human genome editing.
