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Jeffrey M. Levsky,Shailesh M. Shenoy,Rossanna C. Pezo,Robert H. Singer*
A key goal of biology is to relate the expression of specific
genes to a particular cellular phenotype. However, current assaysfor
gene expression destroy the structural context. By combiningadvances
in computational fluorescence microscopy with multiplexprobe design,
we devised technology in which the expression ofmany genes can be
visualized simultaneously inside single cellswith high spatial and
temporal resolution. Analysis of 11 genesin serum-stimulated cultured
cells revealed unique patterns ofgene expression within individual
cells. Using the nucleus asthe substrate for parallel gene analysis,
we provide a platformfor the fusion of genomics and cell biology:
"cellular genomics."
Department of Anatomy and Structural Biology, Albert Einstein
College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
*
To whom correspondence should be addressed. E-mail:
rhsinger{at}aecom.yu.edu
Single-Cell Transcription Site Activation Predicts Chemotherapy Response in Human Colorectal Tumors.
R. C. Pezo, S. J. Gandhi, L. A. Shirley, R. G. Pestell, L. H. Augenlicht, and R. H. Singer (2008)
Cancer Res.
68, 4977-4982
|Abstract »|Full Text »|PDF »
Similar active genes cluster in specialized transcription factories.
A Transcription-dependent Micrococcal Nuclease-resistant Fragment of the Urokinase-type Plasminogen Activator Promoter Interacts with the Enhancer.
C. Ferrai, D. Munari, P. Luraghi, L. Pecciarini, M. G. Cangi, C. Doglioni, F. Blasi, and M. P. Crippa (2007)
J. Biol. Chem.
282, 12537-12546
|Abstract »|Full Text »|PDF »
Gene expression profiling of single cells on large-scale oligonucleotide arrays.
Transcription factor profiling in individual hematopoietic progenitors by digital RT-PCR.
L. Warren, D. Bryder, I. L. Weissman, and S. R. Quake (2006)
PNAS
103, 17807-17812
|Abstract »|Full Text »|PDF »
Single-Cell Analysis of Glucocorticoid Receptor Action Reveals that Stochastic Post-Chromatin Association Mechanisms Regulate Ligand-Specific Transcription.
T. C. Voss, S. John, and G. L. Hager (2006)
Mol. Endocrinol.
20, 2641-2655
|Abstract »|Full Text »|PDF »
Folding and organization of a contiguous chromosome region according to the gene distribution pattern in primary genomic sequence.
L. S. Shopland, C. R. Lynch, K. A. Peterson, K. Thornton, N. Kepper, J. v. Hase, S. Stein, S. Vincent, K. R. Molloy, G. Kreth, et al. (2006)
J. Cell Biol.
174, 27-38
|Abstract »|Full Text »|PDF »
Microfluidic Techniques for Single-Cell Protein Expression Analysis.
E. Fitzpatrick, S. McBride, J. Yavelow, S. Najmi, P. Zanzucchi, and R. Wieder (2006)
Clin. Chem.
52, 1080-1088
|Abstract »|Full Text »|PDF »
Live-Cell Characterization and Analysis of a Clinical Isolate of Bovine Respiratory Syncytial Virus, Using Molecular Beacons.
P. Santangelo, N. Nitin, L. LaConte, A. Woolums, and G. Bao (2006)
J. Virol.
80, 682-688
|Abstract »|Full Text »|PDF »
Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels.
M. Bengtsson, A. Stahlberg, P. Rorsman, and M. Kubista (2005)
Genome Res.
15, 1388-1392
|Abstract »|Full Text »|PDF »
Microgenomics: gene expression analysis at the tissue-specific and single-cell levels.
Quantitative kinetic analysis of nucleolar breakdown and reassembly during mitosis in live human cells.
A. K. L. Leung, D. Gerlich, G. Miller, C. Lyon, Y. W. Lam, D. Lleres, N. Daigle, J. Zomerdijk, J. Ellenberg, and A. I. Lamond (2004)
J. Cell Biol.
166, 787-800
|Abstract »|Full Text »|PDF »
Single-Cell Microbiology: Tools, Technologies, and Applications.
B. F. Brehm-Stecher and E. A. Johnson (2004)
Microbiol. Mol. Biol. Rev.
68, 538-559
|Abstract »|Full Text »|PDF »
Multiplex Detection of RNA Expression in Drosophila Embryos.
D. Kosman, C. M. Mizutani, D. Lemons, W. G. Cox, W. McGinnis, and E. Bier (2004)
Science
305, 846
|Abstract »|Full Text »|PDF »
Surface {micro} Heavy Chain Signals Down-Regulation of the V(D)J-Recombinase Machinery in the Absence of Surrogate Light Chain Components.
G. R. Galler, C. Mundt, M. Parker, R. Pelanda, I.-L. Martensson, and T. H. Winkler (2004)
J. Exp. Med.
199, 1523-1532
|Abstract »|Full Text »|PDF »
Methods for Transcriptional Profiling in Plants. Be Fruitful and Replicate.
B. C. Meyers, D. W. Galbraith, T. Nelson, and V. Agrawal (2004)
Plant Physiology
135, 637-652
|Full Text »|PDF »
K. L. Gunderson, S. Kruglyak, M. S. Graige, F. Garcia, B. G. Kermani, C. Zhao, D. Che, T. Dickinson, E. Wickham, J. Bierle, et al. (2004)
Genome Res.
14, 870-877
|Abstract »|Full Text »|PDF »
Peptide-linked molecular beacons for efficient delivery and rapid mRNA detection in living cells.
N. Nitin, P. J. Santangelo, G. Kim, S. Nie, and G. Bao (2004)
Nucleic Acids Res.
32, e58
|Abstract »|Full Text »|PDF »
Differentiation-induced Colocalization of the KH-type Splicing Regulatory Protein with Polypyrimidine Tract Binding Protein and the c-src Pre-mRNA.
The Transcriptome Profile of Human Embryonic Stem Cells as Defined by SAGE.
M. Richards, S.-P. Tan, J.-H. Tan, W.-K. Chan, and A. Bongso (2004)
Stem Cells
22, 51-64
|Abstract »|Full Text »|PDF »
Phenotypic and Transcriptional Plasticity Directed by a Yeast Mitogen-Activated Protein Kinase Network.
A. Breitkreutz, L. Boucher, B.-J. Breitkreutz, M. Sultan, I. Jurisica, and M. Tyers (2003)
Genetics
165, 997-1015
|Abstract »|Full Text »|PDF »
Ex vivo characterization of human CD8+ T subsets with distinct replicative history and partial effector functions.
N. Rufer, A. Zippelius, P. Batard, M. J. Pittet, I. Kurth, P. Corthesy, J.-C. Cerottini, S. Leyvraz, E. Roosnek, M. Nabholz, et al. (2003)
Blood
102, 1779-1787
|Abstract »|Full Text »|PDF »
Fluorescence in situ hybridization: past, present and future.
Application of Gene Expression Profiling to Colon Cell Maturation, Transformation and Chemoprevention.
L. H. Augenlicht, A. Velcich, L. Klampfer, J. Huang, G. Corner, M. Aranes, C. Laboisse, B. Rigas, M. Lipkin, K. Yang, et al. (2003)
J. Nutr.
133, 2410S-2416
|Abstract »|Full Text »|PDF »
Genome Function and Nuclear Architecture: From Gene Expression to Nanoscience.
T. P. O'Brien, C. J. Bult, C. Cremer, M. Grunze, B. B. Knowles, J. Langowski, J. McNally, T. Pederson, J. C. Politz, A. Pombo, et al. (2003)
Genome Res.
13, 1029-1041
|Abstract »|Full Text »|PDF »
Multicolor Deconvolution Microscopy of Thick Biological Specimens.
C. Maierhofer, R. Gangnus, J. Diebold, and M. R. Speicher (2003)
Am. J. Pathol.
162, 373-379
|Abstract »|Full Text »|PDF »
Novel Detection and Differential Utilization of a c-myc Transcriptional Block in Colon Cancer Chemoprevention.
A. J. Wilson, A. Velcich, D. Arango, A. R. Kurland, S. M. Shenoy, R. C. Pezo, J. M. Levsky, R. H. Singer, and L. H. Augenlicht (2002)
Cancer Res.
62, 6006-6010
|Abstract »|Full Text »|PDF »