Rudolf Jaenisch

Grace X. Y. Zheng

Arvind Ravi

J. Mauro Calabrese

Lea A. Medeiros

Oktay Kirak

Lucas M. Dennis

Christopher B. Burge

Phillip A. Sharp

Abstract: MicroRNAs (miRNAs) post-transcriptionally regulate the expression of thousands of distinct mRNAs. While some regulatory interactions help to maintain basal cellular functions, others are likely relevant in more specific settings, such as response to stress. Here we describe such a role for the mir-290-295 cluster, the dominant miRNA cluster in mouse embryonic stem cells (mESCs). Examination of a target list generated from bioinformatic prediction, as well as expression data following miRNA loss, revealed strong enrichment for apoptotic regulators, two of which we validated directly: Caspase 2, the most highly conserved mammalian caspase, and Ei24, a p53 transcriptional target. Consistent with these predictions, mESCs lacking miRNAs were more likely to initiate apoptosis following genotoxic exposure to gamma irradiation or doxorubicin. Knockdown of either candidate partially rescued this pro-apoptotic phenotype, as did transfection of members of the mir-290-295 cluster. These findings were recapitulated in a specific mir-290-295 deletion line, confirming that they reflect miRNA functions at physiological levels. In contrast to the basal regulatory roles previously identified, the pro-survival phenotype shown here may be most relevant to stressful gestations, where pro-oxidant metabolic states induce DNA damage. Similarly, this cluster may mediate chemotherapeutic resistance in a neoplastic context, making it a useful clinical target

A Latent Pro-survival Function for the Mir-290-295 Cluster in Mouse Embryonic Stem Cells

Robert Lanza

Michael West

Ian Sir Wilmut

Jose Cibelli

John Gurdon

Keith H.S. Campbell

Principles of Cloning, Second Edition is the fully revised edition of the authoritative book on the science of cloning. The book presents the basic biological mechanisms of how cloning works and progresses to discuss current and potential applications in basic biology, agriculture, biotechnology, and medicine. Beginning with the history and theory behind cloning, the book goes on to examine methods of micromanipulation, nuclear transfer, genetic modification, and pregnancy and neonatal care of cloned animals. The cloning of various species—including mice, sheep, cattle, and non-mammals—is considered as well. The Editors have been involved in a number of breakthroughs using cloning technique, including the first demonstration that cloning works in differentiated cells done by the Recipient of the 2012 Nobel Prize for Physiology or Medicine – Dr John Gurdon; the cloning of the first mammal from a somatic cell – Drs Keith Campbell and Ian Wilmut; the demonstration that cloning can reset the biological clock - Drs Michael West and Robert Lanza; the demonstration that a terminally differentiated cell can give rise to a whole new individual – Dr Rudolf Jaenisch and the cloning of the first transgenic bovine from a differentiated cell – Dr Jose Cibelli. The majority of the contributing authors are the principal investigators on each of the animal species cloned to date and are expertly qualified to present the state-of-the-art information in their respective areas. First and most comprehensive book on animal cloning, 100% revised Describes an in-depth analysis of current limitations of the technology and research areas to explore Offers cloning applications on basic biology, agriculture, biotechnology, and medicine

Principles of Cloning

Fred Gage

Feng Zhang

This book is open access under a CC BY 4.0 license. CRISPR-Cas9 is a rapid, efficient, versatile and relatively cheap method for dissecting the molecular pathways that are the basis of life, as well as for investigating and potentially rectifying faults in these pathways that result in disease. This book reviews how CRISPR-Cas9 and other genome editing techniques are advancing our understanding of development and function in the nervous system, uncovering the molecular causes of neurological disorders and providing tools for gene therapy.

Genome Editing in Neurosciences

Rudolf Jaenisch

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