Stem Cell Biology and Regenerative Medicine

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1 Stem Cell Biology and Regenerative Medicine Series Editor Kursad Turksen, Ph.D. For other titles published in this series, go to

2 Donald G. Phinney Editor Adult Stem Cells Biology and Methods of Analysis

3 Editor Donald G. Phinney The Scripps Research Institute Department of Molecular Therapeutics 130 Scripps Way Jupiter, FL USA ISBN e-isbn DOI / Springer New York Dordrecht Heidelberg London Library of Congress Control Number: Springer Science+Business Media, LLC 2011 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Humana Press is part of Springer Science+Business Media (

4 Preface Recent advances in stem cell research include the discovery of stem/progenitor cell populations resident in many adult tissues and organs. However, efforts to validate the stem cell-like nature of these populations have been hampered by the fact that many archetypal assays established to study hematopoietic stem cells, such as competitive repopulation and serial transplantation assays, are not applicable beyond the hematopoietic system. This has mandated the development of surrogate assays to discriminate stem from progenitor and somatic cells. These include quantifying the replicative life span of cells cultured in vitro, their capacity to grow at clonal density, exclude specific DNA binding dyes, express telomerase and/or other pluripotency-related genes, and undergo multilineage differentiation. However, because the mechanisms regulating cell proliferation, life span, self-renewal, and senescence are inextricably intertwined, distinguishing between stem, progenitor, and somatic cells based on their in vitro characteristics is often more difficult than anticipated. Therefore, the goal of this volume is to provide a current overview of adult stem cell biology, describe and critically evaluate methods used to assess stem cell self-renewal, and distinguish this process from other aspects of cell survival, such as regulation of life span, senescence, and immortalization at a molecular level. By providing a comprehensive and critical overview of the biology and methods used to characterize adult stem cells, the volume will serve as a valuable resource for both established scientists and those just entering the field of stem cell biology. Jupiter, FL Donald G. Phinney v

5 Contents Part I 1 Basic Biology of Adult Stem Cells Molecular Mechanisms Regulating Adult Stem Cell Self-Renewal... David M. Panchision 3 2 Maintenance of Adult Stem Cells: Role of the Stem Cell Niche... Yoshiko Matsumoto, Hiroko Iwasaki, and Toshio Suda 35 3 The Emerging Role of micrornas in Adult Stem Cells... Jessica M. Shookhoff and G. Ian Gallicano 57 4 Expression and Function of Pluripotency Genes in Adult Stem Cells... Antonio Lo Nigro, Philip Roelandt, and Catherine M. Verfaillie 5 95 Adult Stem Cell Plasticity Revisited Eva Mezey Part II Characterization of Adult Stem Cells 6 Lineage Tracing of Tissue-Specific Stem Cells In Vivo Kurtis T. Sobush, Keitaro Matsumoto, Huaiyong Chen, and Barry R. Stripp 7 Surrogate Measures of Adult Stem Cell Self-Renewal: The Neural Stem Cell Paradigm Loic P. Deleyrolle, Brent A. Reynolds, and Florian A. Siebzehnrubl 8 ABC Transporters, Aldehyde Dehydrogenase, and Adult Stem Cells Naomi J. Guppy, Linda J. Nicholson, and Malcolm R. Alison vii

6 viii Contents Part III Regulation of Life Span and Immortalization 9 Regulation of Life Span in Adult Stem Cells Philip Davy and Rich Allsopp 10 The Cancer Stem Cell Paradigm Christine E. Eyler, John M. Heddleston, Serendipity Rhinos, Masahiro Hitomi, Olga Guryanova, Will Flavahan, Anita Hjelmeland, and Jeremy Rich Name Index Subject Index

7 Contributors Malcolm R. Alison Centre for Diabetes, Blizard Institute of Cell and Molecular Science, Queen Mary University of London, 4 Newark Street, London, E1 4AT, UK Rich Allsopp Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, BSB Room 163B, Honolulu, HI 96813, USA Huaiyong Chen Department of Medicine, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC 27710, USA Philip Davy Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, BSB Room 163B, Honolulu, HI 96813, USA Loic P. Deleyrolle Department of Neurosurgery, McKnight Brain Institute, University of Florida, 100 Newell Drive, Gainesville, FL 32610, USA Christine E. Eyler Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA William A. Flavahan G. Ian Gallicano Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Medical Dental Building, Room NE205, Washington, DC 20007, USA ix

8 x Contributors Naomi J. Guppy Blizard Institute of Cell and Molecular Science, Barts and London School of Medicine, London, UK Olga A. Guryanova John M. Heddleston Masahiro Hitomi Anita B. Hjelmeland Hiroko Iwasaki Department of Cell Differentiation, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo , Japan Keitaro Matsumoto Department of Medicine, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC 27710, USA Yoshiko Matsumoto Department of Cell Differentiation, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo , Japan Jennifer M. Macswords Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA Eva Mezey National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 49, 5A76 49 Convent Drive, Bethesda, MD 20892, USA Linda J. Nicholson Division of Cancer Studies, King s College, London, UK Antonio Lo Nigro Stem Cell Institute Leuven, Katholieke Universiteit Leuven, Leuven, Belgium

9 Contributors xi David M. Panchision Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD , USA Brent A. Reynolds Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, FL, USA Serendipity Rhinos Jeremy N. Rich Philip Roelandt Stem Cell Institute Leuven, Katholieke Universiteit Leuven, Leuven, Belgium Jessica M. Shookhoff Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Medical Dental Building, Room NE205, Washington, DC 20007, USA Florian A. Siebzehnrubl Department of Neuroscience, McKnight Brain Institute, University of Florida, 100 Newell Drive, Gainesville, FL 32610, USA Kurtis T. Sobush Department of Pediatrics, Division of Pediatric Pulmonary and Sleep Medicine, Duke University Medical Center, DUMC, , Durham, NC, USA Barry R. Stripp Department of Medicine, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC 27710, USA; Department of Cell Biology, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Box DUMC, Durham, NC 27710, USA Toshio Suda Department of Cell Differentiation, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo , Japan Catherine M. Verfaillie Stem Cell Institute Campus Gasthuisberg, Katholieke Universiteit Leuven, Herestraat 49 box 804, 3000 Leuven, Belgium

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