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Author: Albert C. Huang
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Cell fate determination, the process of transforming a unicellular embryonic cell into lineage-restricted specific tissues of a multicellular organism, is fundamental to the process of development. Following the division of a single zygote, how can seemingly similar neighboring cells ultimately differentiate into disparate cell fates, and maintain their differences? An understanding of this complex and intricate process is important for stem cell-based therapies and treatment of cancer. To provide the necessary conceptual background, we review two complementary perspectives that aid our understanding of the differentiation process -- a systems dynamics level view and a molecular mechanism level view. We introduce the experimental systems, the diverse types of data collected for this work, and computational methods to integrate them to arrive at a coherent model. From a systems dynamics perspective, cell fates can be thought of as attractors in the high dimensional gene regulatory networks. With this view, we designed experiments that identified a class of genes that are "divergent" in their expression during the differentiation process. These genes are associated with neutrophil differentiation and cell cycle progression. Further promoter-based transcription factor binding site analyses reveal enrichment of factors functionally linked to cancer progression and neutrophil differentiation, suggesting a systems dynamics view has the potential to elucidate mechanistic level details. From a molecular mechanistic perspective, we investigate how T-bet, a Th1 lineage defining transcription factor, functionally regulates its target genes. We experimentally determine genome-wide binding locations of T-bet and target genes that it regulates. We find distinct genomic signal patterns for genes that are differentially regulated compared to those that are not. We find that the chromatin-modifying and N-terminal domains of the T-bet protein are necessary for the regulation of T-bet targets. Further, T-bet targets are also differentially regulated in other T helper subtypes. Both perspectives offer unique insights into the differentiation process. Future direction would include methods to combine both perspectives by modeling mechanistic details while keeping track of the larger dynamic "emergent" attractor properties of the network.
Author: Albert C. Huang
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Cell fate determination, the process of transforming a unicellular embryonic cell into lineage-restricted specific tissues of a multicellular organism, is fundamental to the process of development. Following the division of a single zygote, how can seemingly similar neighboring cells ultimately differentiate into disparate cell fates, and maintain their differences? An understanding of this complex and intricate process is important for stem cell-based therapies and treatment of cancer. To provide the necessary conceptual background, we review two complementary perspectives that aid our understanding of the differentiation process -- a systems dynamics level view and a molecular mechanism level view. We introduce the experimental systems, the diverse types of data collected for this work, and computational methods to integrate them to arrive at a coherent model. From a systems dynamics perspective, cell fates can be thought of as attractors in the high dimensional gene regulatory networks. With this view, we designed experiments that identified a class of genes that are "divergent" in their expression during the differentiation process. These genes are associated with neutrophil differentiation and cell cycle progression. Further promoter-based transcription factor binding site analyses reveal enrichment of factors functionally linked to cancer progression and neutrophil differentiation, suggesting a systems dynamics view has the potential to elucidate mechanistic level details. From a molecular mechanistic perspective, we investigate how T-bet, a Th1 lineage defining transcription factor, functionally regulates its target genes. We experimentally determine genome-wide binding locations of T-bet and target genes that it regulates. We find distinct genomic signal patterns for genes that are differentially regulated compared to those that are not. We find that the chromatin-modifying and N-terminal domains of the T-bet protein are necessary for the regulation of T-bet targets. Further, T-bet targets are also differentially regulated in other T helper subtypes. Both perspectives offer unique insights into the differentiation process. Future direction would include methods to combine both perspectives by modeling mechanistic details while keeping track of the larger dynamic "emergent" attractor properties of the network.
Author:
Publisher: Academic Press
ISBN: 0128043350
Category : Science
Languages : en
Pages : 347
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Book Description
Cell Fate in Mammalian Development, Volume 128, the latest release in the Current Topics in Developmental Biology series, provides reviews on cell fate in mammalian development. Each chapter is written by an international board of authors, with this release including sections on the Specification of extra-embryonic lineages during mouse pre-implantation development, Cell polarity and fate specification, The circuitry that drives trophectoderm identity, Breaking symmetry and the dynamics of transcription factors directing cell fate specification, Mechanics and cell fate, How physical properties of cells change in development and their effect on cell fate decisions, and more. Provides the authority and expertise of leading contributors from an international board of authors Includes new sections on the specification of extra-embryonic lineages during mouse pre-implantation development, cell polarity and fate specification, the circuitry that drives trophectoderm identity, and more Presents the latest release in the Current Topics in Developmental Biology series
Author: Carlos Simón
Publisher: Cambridge University Press
ISBN: 1107034477
Category : Medical
Languages : en
Pages : 199
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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.
Author: C H (Conrad Hal) 1905- Waddington
Publisher: Legare Street Press
ISBN: 9781022884168
Category :
Languages : en
Pages : 0
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Book Description
C.H. Waddington, one of the most prominent geneticists of the twentieth century, provides a clear and concise overview of modern genetics in this landmark book. From DNA to epigenetics, Waddington covers the full breadth of the field, making this an essential read for students and professionals in genetics and related fields. This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work is in the "public domain in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant.
Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309170427
Category : Science
Languages : en
Pages : 112
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Book Description
Recent scientific breakthroughs, celebrity patient advocates, and conflicting religious beliefs have come together to bring the state of stem cell researchâ€"specifically embryonic stem cell researchâ€"into the political crosshairs. President Bush's watershed policy statement allows federal funding for embryonic stem cell research but only on a limited number of stem cell lines. Millions of Americans could be affected by the continuing political debate among policymakers and the public. Stem Cells and the Future of Regenerative Medicine provides a deeper exploration of the biological, ethical, and funding questions prompted by the therapeutic potential of undifferentiated human cells. In terms accessible to lay readers, the book summarizes what we know about adult and embryonic stem cells and discusses how to go about the transition from mouse studies to research that has therapeutic implications for people. Perhaps most important, Stem Cells and the Future of Regenerative Medicine also provides an overview of the moral and ethical problems that arise from the use of embryonic stem cells. This timely book compares the impact of public and private research funding and discusses approaches to appropriate research oversight. Based on the insights of leading scientists, ethicists, and other authorities, the book offers authoritative recommendations regarding the use of existing stem cell lines versus new lines in research, the important role of the federal government in this field of research, and other fundamental issues.
Author: Junyue Cao
Publisher:
ISBN:
Category :
Languages : en
Pages : 322
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Book Description
Animal development is one of the greatest sources of wonders in science. Development of multicellular organism is characterized by the differentiation of a fertilized egg into diverse cell types of the body in a programed temporal spatial order. The process of development includes fertilization, cleavage, gastrulation, organogenesis, metamorphosis, regeneration, and senescence. Characterizing cell differentiation in each step, by resolving the cell state diversity and cell fate dynamics, is the key to fully understanding developmental process. The expression levels of mRNA species are readily linked to cellular function, and therefore profiling the transcriptome of individual cells has emerged as a powerful strategy for resolving cell state heterogeneity. However, current methods for single cell RNA sequencing all rely on the isolation of individual cells within physical compartments and thus have problems such as low throughput, high cost, and information lost from other molecular layers. During the three and half years of my graduate study, I developed four novel high-throughput single cell genomic techniques to get over these limitations and applied them to profiling cell state heterogeneity and dynamics in development at single cell resolution. To resolve cellular state heterogeneity, I developed a combinatorial indexing strategy to profile the transcriptome across tens of thousands of single cells (sci-RNA-seq: Single cell Combinatorial Indexing RNA sequencing), and applied sci-RNA-seq to generate the first catalog of single cell transcriptomes at the scale of whole organism Caenorhabditis elegans (Cao. J., Jonathan. P., et al, Comprehensive single-cell transcriptional profiling of a multicellular organism, Science, 2017). I profiled over 50,000 cells from the nematode C. elegans at the L2 stage, which is over 50-fold "shotgun cellular coverage" of its somatic cell composition. This is the first study to show that single cell transcriptome alone is sufficient to separate all major cell types from whole animal. Cell type specific genes for 27 distinct cell types are identified, including for some fine-grained cell types that are present in only one or two cells per individual. Given that C.elegans is the only organism with a fully mapped cellular lineage, these data represent a rich resource for future research aimed at defining cell types and states. The dataset will advance our understanding of developmental biology, and constitute a major step towards a comprehensive, single-cell molecular atlas of a whole animal. To further characterize cellular state across multiple molecular layers, I developed sci-CAR, the first high throughput single cell genomic approach that can jointly profile epigenome (chromatin accessibility) and transcriptome in each of 1000s of single cells (Cao. J. et al, Joint profiling of chromatin accessibility and gene expression in thousands of single cells, Science, 2018). I applied sci-CAR to 11,233 cells from whole mouse kidney and linked cis-regulatory sites to their putative target genes based on the covariance of chromatin accessibility and transcription at the single-cell level. To the best of our knowledge, this represents the first joint profiling of the epigenome and transcriptome in individual cells at the scale and complexity of a whole mammalian organ. One critical challenge in development is to characterize the cell differentiation path for all major cell types forming our body. During mammalian organogenesis, the cells of the three germ layers transform into an embryo that includes most major internal and external organs. The key regulators of developmental defects can be studied during this critical window, but conventional approaches lack the throughput and resolution to obtain a global view of the molecular states and trajectories of a rapidly diversifying and expanding number of cell types. To investigate cell state dynamics in this critical window, I developed another single cell transcriptome profiling technique (sci-RNA-seq3), the first single cell RNA-seq technique capable of profiling millions of single cells in a single experiment, with over one hundred times higher throughput and lower cost compared with conventional approaches. I applied sci-RNA-seq3 to profiling ~ 2 million cells derived from 61 mouse embryos staged between 9.5 and 13.5 days of gestation (Cao. J., Spielmann. M., et al, The single-cell transcriptional landscape of mammalian organogenesis, Nature, 2018). This is by far the most comprehensive cell atlas of mammalian development as well as the largest single cell RNA-seq data set in the world. By unsupervised clustering analysis, I characterized hundreds of expanding, contracting and transient cell types, many of which are only detected because of the depth of cellular coverage obtained here, and defined the corresponding sets of cell type-specific marker genes, several of which are validated by whole mount in situ hybridization. With a new single cell RNA-seq analysis package Monocle 3, I further delineated and annotated 56 single cell developmental trajectories of mouse organogenesis, spanning all major systems such as central nervous system and reproductive system. The dynamics of cell proliferation and key gene regulators within each cell lineage are further identified. These data comprise a foundational resource for single cell genomic field and mammalian developmental biology. To further characterizing the mechanism regulating cell state dynamics, I developed sci-fate, the first strategy to recover whole transcriptome temporal dynamics across thousands of single cells (Cao. J., et al, Characterizing single cell temporal dynamics with sci-fate, manuscript in preparation, 2019). I applied sci-fate to a model system of cortisol response and developed a computation strategy to identify key driving transcription factors regulating cell state changes. Based on the data, I built a cell state transition network for future cell state prediction, and illustrate key factors regulating cell state transition dynamics. This is the first study to quantitatively characterize cell state dynamics at whole transcriptome level and constitutes a major step to fully understanding mechanisms in cell fate determination.
Author: C.H. Waddington
Publisher: Routledge
ISBN: 1317657543
Category : History
Languages : en
Pages : 231
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Book Description
First published in 1957, this essential classic work bridged the gap between analytical and theoretical biology, thus setting the insights of the former in a context which more sensitively reflects the ambiguities surrounding many of its core concepts and objectives. Specifically, these five essays are concerned with some of the major problems of classical biology: the precise character of biological organisation, the processes which generate it, and the specifics of evolution. With regard to these issues, some thinkers suggest that biological organisms are not merely distinguishable from inanimate ‘things’ in terms of complexity, but are in fact radically different qualitatively: they exemplify some constitutive principle which is not elsewhere manifested. It is the desire to bring such ideas into conformity with our understanding of analytical biology which unifies these essays. They explore the contours of a conceptual framework sufficiently wide to embrace all aspects of living systems.
Author: Janet Rossant
Publisher: Gulf Professional Publishing
ISBN: 9780125979511
Category : Medical
Languages : en
Pages : 754
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Book Description
This book represents a classic compilation of current knowledge about mouse development and its correlates to research in cell biology, molecular biology, genetics, and neuroscience. Emphasis is placed on the research strategy, experimental design, and critical analysis of the data, disguishing this from other books that only focus on protocols for mouse developmental research. Selected chapters are indexed to electronic databases such as GeneBank, GenBank, Electronic Mouse Atlas, and Transgenic/Knockout, further increasing the utility of this book as a reference. *Broad-based overview of mouse development from fundamental to specialist levels *Extensive coverage of a wide range of developmental mutations of the mouse *Excellent benchmark illustrations of brain, craniofacial, gut and heart development *In-depth experiment-based assessment of concepts in mammalian development *Focus on models of specific relevance to human development *Comprehensive reference to key literature and electronic databases related to mouse development *High-quality full-color production
Author: Jean-Pierre Tassan
Publisher: Springer
ISBN: 3319531506
Category : Science
Languages : en
Pages : 421
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Book Description
This book provides readers with an overview of the frequent occurrence of asymmetric cell division. Employing a broad range of examples, it highlights how this mode of cell division constitutes the basis of multicellular organism development and how its misregulation can lead to cancer. To underline such developmental correlations, readers will for example gain insights into stem cell fate and tumor growth. In turn, subsequent chapters include descriptions of asymmetric cell division from unicellular organisms to humans in both physiological and pathological conditions. The book also illustrates the importance of this process for evolution and our need to understand the background mechanisms, offering a valuable guide not only for students in the field of developmental biology but also for experienced researchers from neighboring fields.
Author: August Weismann
Publisher:
ISBN:
Category : Genetics
Languages : en
Pages : 524
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Book Description
