Chemical and Functional Genomic Approaches to Stem Cell
Biology and Regenerative Medicine 1st Edition
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CHEMICAL AND
FUNCTIONAL GENOMIC
APPROACHES TO STEM
CELL BIOLOGY AND
REGENERATIVE
MEDICINE
Edited by
SHENG DING
Departments of Chemistry and Cell Biology
The Scripps Research Institute
A JOHN WILEY & SONS, INC., PUBLICATION
Copyright # 2008 by John Wiley & Sons, Inc. All rights reserved.
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Library of Congress Cataloging-in-Publication Data:
Chemical and functional genomic approaches to stem cell biology and regenerative
medicine / [edited by] Sheng Ding.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-470-04146-8 (cloth)
1. Stem cells–Research–Methodology. 2. Physiological genomics.
3. Molecular genetics. I. Ding, Sheng, 1975-
[DNLM: 1. Genomics. 2. Regenerative Medicine–methods. 3. Stem Cells.
QU 58.5 C5165 2008] QH588.S83C455 2008
6160 .02774–dc22 2007039335
Printed in the United States of America
10 9 8 7 6 5 4 3 2 1
CONTENTS
Contributors vii
1 Embryonic Stem Cells 1
Crystal L. Sengstaken, Eric N. Schulze, and Qi-Long Ying
2 Adult Stem Cells 27
Lief Fenno and Chad A. Cowan
3 Genomewide Expression Analysis Technologies 59
John R. Walker
4 Genomic cDNA and RNAi Functional Profiling and Its
Potential Application to the Study of Mammalian Stem Cells 83
Jia Zhang, Myleen Medina, Genevieve Welch, Deanna Shumate,
Anthony Marelli, and Anthony P. Orth
5 Chemical Technologies: Probing Biology with
Small Molecules 109
Nicolas Winssinger, Zbigniew Pianowski, and Sofia Barluenga
6 Protein Characterization by Biological Mass Spectrometry 145
Venkateshwar A. Reddy and Eric C. Peters
7 Large-Scale Genomic Analysis of Stem Cell Populations 169
Jonathan D. Chesnut and Mahendra S. Rao
v
vi CONTENTS
8 Exploring Stem Cell Biology with Small Molecules
and Functional Genomics 187
Julie Clark, Yue Xu, Simon Hilcove, and Sheng Ding
9 Regeneration Screens in Model Organisms 207
Chetana Sachidanandan and Randall T. Peterson
10 Proteomics in Stem Cells 223
Qiang Tian and W. Andy Tao
Index 243
CONTRIBUTORS
Sofia Barluenga, Organic and Bioorganic Chemistry Laboratory, Institut de
Science et Ingenierie Supramolecularies, Universite Louis Pasteur, 8 allee
Gaspard Monge 67000, Strasbourg, France
*Jonathan D. Chesnut, Stem Cells and Regenerative Medicine, Invitrogen Cor-
poration, Carlsbad, CA 92008 (
[email protected])
Julie Clark, Department of Chemistry and the Skaggs Institute for Chemical Biol-
ogy, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla,
CA 92037
*Chad A. Cowan, Stowers Medical Institute, Center for Regenerative Medicine
and Technology, Cardiovascular Research Center, 185 Cambridge St., Boston,
MA 02114 (
[email protected])
*Sheng Ding, Department of Chemistry and the Skaggs Institute for Chemical
Biology, The Scripps Research Institute, 10550 North Torrey Pines Road,
La Jolla, CA 92037 (
[email protected])
Lief Fenno, Stowers Medical Institute, Center for Regenerative Medicine and
Technology, Cardiovascular Research Center, 185 Cambridge St., Boston, MA
02114
Simon Hilcove, Department of Chemistry and the Skaggs Institute for Chemical
Biology, The Scripps Research Institute, 10550 North Torrey Pines Road,
La Jolla, CA 92037
Anthony Marelli, Genomics Institute of the Novartis Research Foundation, 10675
John Jay Hopkins Drive, San Diego, CA 92121
vii
viii CONTRIBUTORS
Myleen Medina, Genomics Institute of the Novartis Research Foundation, 10675
John Jay Hopkins Drive, San Diego, CA 92121
*Anthony P. Orth, Genomics Institute of the Novartis Research Foundation,
10675 John Jay Hopkins Drive, San Diego, CA 92121 (
[email protected])
*Eric C. Peters, Genomics Institute of the Novartis Research Foundation, 10675
John Jay Hopkins Drive, San Diego, CA 92121(
[email protected])
*Randall T. Peterson, Cardiovascular Research Center, Massachusetts General
Hospital and Harvard Medical School, Boston, MA (
[email protected].
harvard.edu)
Zbigniew Pianowski, Organic and Bioorganic Chemistry Laboratory, Institut de
Science et Ingenierie Supramolecularies, Universite Louis Pasteur, 8 allee
Gaspard Monge 67000, Strasbourg, France
Mahendra S. Rao, Stem Cells and Regenerative Medicine, Invitrogen Corpora-
tion, Carlsbad, CA 92008
Venkateshwar A. Reddy, Genomics Institute of the Novartis Research Foundation,
10675 John Jay Hopkins Drive, San Diego, CA 92121
Chetana Sachidanandan, Cardiovascular Research Center, Massachustetts Gen-
eral Hospital and Harvard Medical School, Boston, MA
Eric N. Schulze, Center for Stem Cell and Regenerative Medicine, Department
of Cell and Neurobiology, Keck School of Medicine, University of Southern
California, 1501 San Pablo Street, Los Angeles, CA 90033
Crystal L. Sengstaken, Center for Stem Cell and Regenerative Medicine, Depart-
ment of Cell and Neurobiology, Keck School of Medicine, University of South-
ern California, 1501 San Pablo Street, Los Angeles, CA 90033
Deanna Shumate, Genomics Institute of the Novartis Research Foundation, 10675
John Jay Hopkins Drive, San Diego, CA 92121
W. Andy Tao, Department of Biochemistry, Purdue University, 175 S. University
Street, West Lafayette, IN 47907
*Qiang Tian, Institute for Systems Biology, 1441 North 34th Street, Seattle, WA
98103 (
[email protected])
*John R. Walker, Group Leader, RNA Dynamics, Genomics Institute of the
Novartis Research Foundation, 10675 John J. Hopkins Drive, San Diego, CA
92121 (
[email protected])
Genevieve Welch, Genomics Institute of the Novartis Research Foundation, 10675
John Jay Hopkins Drive, San Diego, CA 92121
*Nicolas Winssinger, Organic and Bioorganic Chemistry Laboratory, Institut de
Science et Ingenierie Supramolecularies, Universite Louis Pasteur, 8 allee
Gaspard Monge 67000, Strasbourg, France (
[email protected])
CONTRIBUTORS ix
Yue Xu, Department of Chemistry and the Skaggs Institute for Chemical Biology,
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA
92037
*Qi-Long Ying, Center for Stem Cell and Regenerative Medicine, Department
of Cell and Neurobiology, Keck School of Medicine, University of Southern
California, 1501 San Pablo Street, Los Angeles, CA 90033 (qying@keck.
usc.edu)
Jia Zhang, Genomics Institute of the Novartis Research Foundation, 10675 John
Jay Hopkins Drive, San Diego, CA 92121
*Corresponding author.
FIGURE 1.3 Differentiation potential of ES cells. ES cells can be induced to differentiate
into all somatic cell lineages via the formation of three-dimensional EBs or monolayer culture.
FIGURE 2.1 Adult stem cell lineages. (See text for full caption.)
FIGURE 2.2 Adult stem cell niche. Adult stem cells are maintained in a specialized
environment known as the niche. (See text for full caption.)
FIGURE 2.3 Discovery of the hematopoietic stem cell. (See text for full caption.)
FIGURE 2.4 Cancer stem cell. Two major theories of the cancer stem cell arise from the
common theme of aberrant self-renewal. (See text for full caption.)
FIGURE 3.1 Differential gene expression technology progression. (See text for full caption.)
FIGURE 5.1 Enabling technologies for automated synthesis (a) and library synthesis (b).
FIGURE 5.2 Cartoon representation of the chemical space. Representation obtained by
plotting the principal component of physicochemical properties on x,y,z axis. Biologically
active compounds tend to cluster into discrete areas (represented by the colored spheres).
(Reprinted with permission from Ref [20]).
FIGURE 5.6 Synthesis and microarraying of a 1,3-dioxane library. Discovery of a selective
Ure2p (transcription factor) modulator.
FIGURE 5.9 Synthesis of libraries targeting protein–protein interactions. Libraries based on
C2-symmetric ligands led to the discovery of an EPO agonist while library of isoindolinones
afforded a Myc-Max protein–protein interaction inhibitor.
