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DOI: 10.1055/s-2006-952155
Genomic Approaches to Early Embryogenesis and Stem Cell Biology
Publication History
Publication Date:
22 November 2006 (online)
ABSTRACT
Large-scale systematic gene expression analyses of early embryos and stem cells provide useful information to identify genes expressed differentially or uniquely in these cells. We review the current status of various approaches applied to preimplantation embryos and stem cells: expressed sequence tag, serial analysis of gene expression, differential display, massively parallel signature sequencing, DNA microarray (DNA chip) analysis, and chromatin-immunoprecipitation microarrays. We also discuss the biological questions that can only be addressed by the analysis of global gene expression patterns, such as so-called stemness and developmental potency. As the emphasis now shifts from expression profiling to functional studies, we review the genome-scale functional studies of genes: expression cloning, gene trapping, RNA interference, and gene disruptions. Finally, we discuss the future clinical application of such methodologies.
KEYWORDS
Microarray - stem cells - preimplantation embryos - embryogenomics - large-scale analysis
REFERENCES
- 1 Cole R J, Edwards R G, Paul J. Cytodifferentiation and embryogenesis in cell colonies and tissue cultures derived from ova and blastocysts of the rabbit. Dev Biol. 1966; 13 385-407
- 2 Evans M J, Kaufman M H. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981; 292 154-156
- 3 Martin G R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA. 1981; 78 7634-7638
- 4 Thomson J A, Itskovitz-Eldor J, Shapiro S S et al.. Embryonic stem cell lines derived from human blastocysts. Science. 1998; 282 1145-1147
- 5 Ko M S. Embryogenomics: developmental biology meets genomics. Trends Biotechnol. 2001; 19 511-518
- 6 Ko M S. An ‘equalized cDNA library’ by the reassociation of short double-stranded cDNAs. Nucleic Acids Res. 1990; 18 5705-5711
- 7 Adams M D, Kelley J M, Gocayne J D et al.. Complementary DNA sequencing: expressed sequence tags and human genome project. Science. 1991; 252 1651-1656
- 8 dbEST: Expressed Sequence Tag Database. Available at: http://www.ncbi.nlm.nih.gov/dbEST/index.html Accessed October 12, 2006
- 9 Stanton J L, Macgregor A B, Green D P. Using expressed sequence tag databases to identify ovarian genes of interest. Mol Cell Endocrinol. 2002; 191 11-14
- 10 Stanton J L, Bascand M, Fisher L et al.. Gene expression profiling of human GV oocytes: an analysis of a profile obtained by serial analysis of gene expression (SAGE). J Reprod Immunol. 2002; 53 193-201
- 11 Stanton J L, Green D P. A set of 840 mouse oocyte genes with well-matched human homologues. Mol Hum Reprod. 2001; 7 521-543
- 12 Stanton J L, Green D P. Meta-analysis of gene expression in mouse preimplantation embryo development. Mol Hum Reprod. 2001; 7 545-552
- 13 Stanton J L, Green D P. A set of 1542 mouse blastocyst and pre-blastocyst genes with well-matched human homologues. Mol Hum Reprod. 2002; 8 149-166
- 14 Ko M S, Kitchen J R, Wang X et al.. Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development. Development. 2000; 127 1737-1749
- 15 Lin Y N, Matzuk M M. High-throughput discovery of germ-cell-specific genes. Semin Reprod Med. 2005; 23 201-212
- 16 Rajkovic A, Yan C, Yan W et al.. Obox, a family of homeobox genes preferentially expressed in germ cells. Genomics. 2002; 79 711-717
- 17 Rajkovic A, Yan M SC, Klysik M, Matzuk M. Discovery of germ cell-specific transcripts by expressed sequence tag database analysis. Fertil Steril. 2001; 76 550-554
- 18 Yan W, Rajkovic A, Viveiros M M et al.. Identification of Gasz, an evolutionarily conserved gene expressed exclusively in germ cells and encoding a protein with four ankyrin repeats, a sterile-alpha motif, and a basic leucine zipper. Mol Endocrinol. 2002; 16 1168-1184
- 19 Yan W, Burns K H, Ma L, Matzuk M M. Identification of Zfp393, a germ cell-specific gene encoding a novel zinc finger protein. Mech Dev. 2002; 118 233-239
-
20 NCBI UniGene Digital Differential Display Tool .Available at: http://www.ncbi.nlm.nih.gov/UniGene/ddd.cgi
- 21 Mitsui K, Tokuzawa Y, Itoh H et al.. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003; 113 631-642
- 22 Maruyama M, Ichisaka T, Nakagawa M, Yamanaka S. Differential roles for Sox15 and Sox2 in transcriptional control in mouse embryonic stem cells. J Biol Chem. 2005; 280 24371-24379
- 23 Takahashi K, Mitsui K, Yamanaka S. Role of ERas in promoting tumour-like properties in mouse embryonic stem cells. Nature. 2003; 423 541-545
- 24 Chambers I, Colby D, Robertson M et al.. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003; 113 643-655
- 25 Bolton J A, Wood S A, Kennedy D et al.. Retinoic acid-dependent upregulation of mouse folate receptor-alpha expression in embryonic stem cells, and conservation of alternative splicing patterns. Gene. 1999; 230 215-224
- 26 Liang P, Pardee A B. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science. 1992; 257 967-971
- 27 Hollnagel A, Oehlmann V, Heymer J et al.. Id genes are direct targets of bone morphogenetic protein induction in embryonic stem cells. J Biol Chem. 1999; 274 19838-19845
- 28 Brown A L, Kay G F. Bex1, a gene with increased expression in parthenogenetic embryos, is a member of a novel gene family on the mouse X chromosome. Hum Mol Genet. 1999; 8 611-619
- 29 Diatchenko L, Lau Y F, Campbell A P et al.. Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc Natl Acad Sci USA. 1996; 93 6025-6030
- 30 Zeng F, Schultz R M. Gene expression in mouse oocytes and preimplantation embryos: use of suppression subtractive hybridization to identify oocyte- and embryo-specific genes. Biol Reprod. 2003; 68 31-39
- 31 Velculescu V E, Zhang L, Vogelstein B, Kinzler K W. Serial analysis of gene expression. Science. 1995; 270 484-487
- 32 Anisimov S V, Tarasov K V, Tweedie D et al.. SAGE identification of gene transcripts with profiles unique to pluripotent mouse R1 embryonic stem cells. Genomics. 2002; 79 169-176
- 33 Richards M, Tan S P, Tan J H et al.. The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells. 2004; 22 51-64
- 34 Brenner S, Johnson M, Bridgham J et al.. Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arrays. Nat Biotechnol. 2000; 18 630-634
- 35 Wei C L, Miura T, Robson P et al.. Transcriptome profiling of human and murine ESCs identifies divergent paths required to maintain the stem cell state. Stem Cells. 2005; 23 166-185
- 36 Miura T, Luo Y, Khrebtukova I et al.. Monitoring early differentiation events in human embryonic stem cells by massively parallel signature sequencing and expressed sequence tag scan. Stem Cells Dev. 2004; 13 694-715
- 37 Komiya T, Tanigawa Y, Hirohashi S. A large-scale in situ hybridization system using an equalized cDNA library. Anal Biochem. 1997; 254 23-30
- 38 Neidhardt L, Gasca S, Wertz K et al.. Large-scale screen for genes controlling mammalian embryogenesis, using high-throughput gene expression analysis in mouse embryos. Mech Dev. 2000; 98 77-94
- 39 Gitton Y, Dahmane N, Baik S et al.. A gene expression map of human chromosome 21 orthologues in the mouse. Nature. 2002; 420 586-590
- 40 Reymond A, Marigo V, Yaylaoglu M B et al.. Human chromosome 21 gene expression atlas in the mouse. Nature. 2002; 420 582-586
- 41 Yoshikawa T, Piao Y, Zhong J et al.. High-throughput screen for genes predominantly expressed in the ICM of mouse blastocysts by whole mount in situ hybridization. Gene Expr Patterns. 2006; 6 213-224
- 42 Rothstein J L, Johnson D, DeLoia J A et al.. Gene expression during preimplantation mouse development. Genes Dev. 1992; 6 1190-1201
- 43 Sasaki N, Nagaoka S, Itoh M et al.. Characterization of gene expression in mouse blastocyst using single-pass sequencing of 3995 clones. Genomics. 1998; 49 167-179
- 44 Sharov A A, Piao Y, Matoba R et al.. Transcriptome analysis of mouse stem cells and early embryos. PLoS Biol. 2003; 1 410-419
- 45 Hwang S Y, Oh B, Knowles B B et al.. Expression of genes involved in mammalian meiosis during the transition from egg to embryo. Mol Reprod Dev. 2001; 59 144-158
- 46 Hamatani T, Daikoku T, Wang H et al.. Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation. Proc Natl Acad Sci USA. 2004; 101 10326-10331
- 47 Wang Q T, Piotrowska K, Ciemerych M A et al.. A genome-wide study of gene activity reveals developmental signaling pathways in the preimplantation mouse embryo. Dev Cell. 2004; 6 133-144
- 48 Zeng F, Baldwin D A, Schultz R M. Transcript profiling during preimplantation mouse development. Dev Biol. 2004; 272 483-496
- 49 Wang S, Cowan C A, Chipperfield H, Powers R D. Gene expression in the preimplantation embryo: in-vitro developmental changes. Reprod Biomed Online. 2005; 10 607-616
- 50 Bermudez M G, Wells D, Malter H et al.. Expression profiles of individual human oocytes using microarray technology. Reprod Biomed Online. 2004; 8 325-337
- 51 Dobson A T, Raja R, Abeyta M J et al.. The unique transcriptome through day 3 of human preimplantation development. Hum Mol Genet. 2004; 13 1461-1470
- 52 Smith A G. Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol. 2001; 17 435-462
- 53 Keller G. Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev. 2005; 19 1129-1155
- 54 Hubner K, Fuhrmann G, Christenson L K et al.. Derivation of oocytes from mouse embryonic stem cells. Science. 2003; 300 1251-1256
- 55 Geijsen N, Horoschak M, Kim K et al.. Derivation of embryonic germ cells and male gametes from embryonic stem cells. Nature. 2004; 427 148-154
- 56 Toyooka Y, Tsunekawa N, Akasu R, Noce T. Embryonic stem cells can form germ cells in vitro. Proc Natl Acad Sci USA. 2003; 100 11457-11462
- 57 Tanaka S, Kunath T, Hadjantonakis A K et al.. Promotion of trophoblast stem cell proliferation by FGF4. Science. 1998; 282 2072-2075
- 58 Carter M G, Piao Y, Dudekula D B et al.. The NIA cDNA project in mouse stem cells and early embryos. C R Biol. 2003; 326 931-940
- 59 Rao R R, Stice S L. Gene expression profiling of embryonic stem cells leads to greater understanding of pluripotency and early developmental events. Biol Reprod. 2004; 71 1772-1778
- 60 Robson P. The maturing of the human embryonic stem cell transcriptome profile. Trends Biotechnol. 2004; 22 609-612
-
61 Tanaka T S, Carter M G, Aiba K, Ko M S.
Genomic approaches to stem cell biology . In: Odorico JS, Pederse RA, Zhang SU Human Embryonic Stem Cells. New York; BIOS Scientific Publishers 2005: 339-361 - 62 Ramalho-Santos M, Yoon S, Matsuzaki Y et al.. “Stemness”: transcriptional profiling of embryonic and adult stem cells. Science. 2002; 298 597-600
- 63 Ivanova N B, Dimos J T, Schaniel C et al.. A stem cell molecular signature. Science. 2002; 298 601-604
- 64 Pesce M, Scholer H R. Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells. 2001; 19 271-278
- 65 Ovitt C E, Scholer H R. The molecular biology of Oct-4 in the early mouse embryo. Mol Hum Reprod. 1998; 4 1021-1031
- 66 Niwa H, Miyazaki J, Smith A G. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet. 2000; 24 372-376
- 67 Jiang Y, Vaessen B, Lenvik T et al.. Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol. 2002; 30 896-904
- 68 Lessard J, Sauvageau G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 2003; 423 255-260
- 69 Molofsky A V, Pardal R, Iwashita T et al.. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature. 2003; 425 962-967
- 70 Park I K, Qian D, Kiel M et al.. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003; 423 302-305
- 71 Fortunel N O, Otu H H, Ng H H et al.. Comment on “‘Stemness’: transcriptional profiling of embryonic and adult stem cells” and “a stem cell molecular signature”. Science. 2003; 302 393
- 72 Evsikov A V, Solter D. Comment on “ ‘Stemness’: transcriptional profiling of embryonic and adult stem cells” and “a stem cell molecular signature”. Science. 2003; 302 393
- 73 Mikkers H, Frisen J. Deconstructing stemness. EMBO J. 2005; 24 2715-2719
- 74 Pyle A D, Donovan P J, Lock L F. Chipping away at ‘stemness’. Genome Biol. 2004; 5 235
- 75 Brazma A, Hingamp P, Quackenbush J et al.. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet. 2001; 29 365-371
- 76 Edgar R, Domrachev M, Lash A E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002; 30 207-210
- 77 Brazma A, Parkinson H, Sarkans U et al.. ArrayExpress-a public repository for microarray gene expression data at the EBI. Nucleic Acids Res. 2003; 31 68-71
- 78 Ikeo K, Ishi-i J, Tamura T et al.. CIBEX: center for information biology gene expression database. C R Biol. 2003; 326 1079-1082
- 79 Yuen T, Wurmbach E, Pfeffer R L et al.. Accuracy and calibration of commercial oligonucleotide and custom cDNA microarrays. Nucleic Acids Res. 2002; 30 e48
- 80 Yauk C L, Berndt M L, Williams A, Douglas G R. Comprehensive comparison of six microarray technologies. Nucleic Acids Res. 2004; 32 e124
- 81 Park P J, Cao Y A, Lee S Y et al.. Current issues for DNA microarrays: platform comparison, double linear amplification, and universal RNA reference. J Biotechnol. 2004; 112 225-245
- 82 Larkin J E, Frank B C, Gavras H et al.. Independence and reproducibility across microarray platforms. Nat Methods. 2005; 2 337-344
- 83 Kuo W P, Jenssen T K, Butte A J et al.. Analysis of matched mRNA measurements from two different microarray technologies. Bioinformatics. 2002; 18 405-412
- 84 Mah N, Thelin A, Lu T et al.. A comparison of oligonucleotide and cDNA-based microarray systems. Physiol Genomics. 2004; 16 361-370
- 85 Tan P K, Downey T J, Spitznagel Jr E L et al.. Evaluation of gene expression measurements from commercial microarray platforms. Nucleic Acids Res. 2003; 31 5676-5684
- 86 Irizarry R A, Warren D, Spencer F et al.. Multiple-laboratory comparison of microarray platforms. Nat Methods. 2005; 2 345-350
- 87 Bammler T, Beyer R P, Bhattacharya S et al.. Standardizing global gene expression analysis between laboratories and across platforms. Nat Methods. 2005; 2 351-356
- 88 Pokholok D K, Harbison C T, Levine S et al.. Genome-wide map of nucleosome acetylation and methylation in yeast. Cell. 2005; 122 517-527
- 89 Boyer L A, Lee T I, Cole M F et al.. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005; 122 947-956
- 90 Masui S, Shimosato D, Toyooka Y et al.. An efficient system to establish multiple embryonic stem cell lines carrying an inducible expression unit. Nucleic Acids Res. 2005; 33 e43
- 91 Hicks G G, Shi E G, Li X M et al.. Functional genomics in mice by tagged sequence mutagenesis. Nat Genet. 1997; 16 338-344
- 92 Zambrowicz B P, Friedrich G A, Buxton E C et al.. Disruption and sequence identification of 2,000 genes in mouse embryonic stem cells. Nature. 1998; 392 608-611
- 93 Skarnes W C, von Melchner H, Wurst W et al.. A public gene trap resource for mouse functional genomics. Nat Genet. 2004; 36 543-544
- 94 Schnutgen F, De-Zolt S, Van Sloun P et al.. Genomewide production of multipurpose alleles for the functional analysis of the mouse genome. Proc Natl Acad Sci USA. 2005; 102 7221-7226
- 95 Chen Y T, Liu P, Bradley A. Inducible gene trapping with drug-selectable markers and Cre/loxP to identify developmentally regulated genes. Mol Cell Biol. 2004; 24 9930-9941
- 96 Hansen J, Floss T, Van Sloun P et al.. A large-scale, gene-driven mutagenesis approach for the functional analysis of the mouse genome. Proc Natl Acad Sci USA. 2003; 100 9918-9922
- 97 Carlson C M, Dupuy A J, Fritz S et al.. Transposon mutagenesis of the mouse germline. Genetics. 2003; 165 243-256
- 98 Friedel R H, Plump A, Lu X et al.. Gene targeting using a promoterless gene trap vector (“targeted trapping”) is an efficient method to mutate a large fraction of genes. Proc Natl Acad Sci USA. 2005; 102 13188-13193
- 99 Forrai A, Robb L. The gene trap resource: a treasure trove for hemopoiesis research. Exp Hematol. 2005; 33 845-856
- 100 Scheel J R, Ray J, Gage F H, Barlow C. Quantitative analysis of gene expression in living adult neural stem cells by gene trapping. Nat Methods. 2005; 2 363-370
- 101 Austin C P, Battey J F, Bradley A et al.. The knockout mouse project. Nat Genet. 2004; 36 921-924
- 102 Kunath T, Gish G, Lickert H et al.. Transgenic RNA interference in ES cell-derived embryos recapitulates a genetic null phenotype. Nat Biotechnol. 2003; 21 559-561
- 103 Vanhecke D, Janitz M. Functional genomics using high-throughput RNA interference. Drug Discov Today. 2005; 10 205-212
- 104 Vanhecke D, Janitz M. High-throughput gene silencing using cell arrays. Oncogene. 2004; 23 8353-8358
- 105 Hsieh A C, Bo R, Manola J et al.. A library of siRNA duplexes targeting the phosphoinositide 3-kinase pathway: determinants of gene silencing for use in cell-based screens. Nucleic Acids Res. 2004; 32 893-901
- 106 Yang S, Tutton S, Pierce E, Yoon K. Specific double-stranded RNA interference in undifferentiated mouse embryonic stem cells. Mol Cell Biol. 2001; 21 7807-7816
- 107 Velkey J M, O'Shea K S. Oct4 RNA interference induces trophectoderm differentiation in mouse embryonic stem cells. Genesis. 2003; 37 18-24
- 108 Pebernard S, Iggo R D. Determinants of interferon-stimulated gene induction by RNAi vectors. Differentiation. 2004; 72 103-111
- 109 Persengiev S P, Zhu X, Green M R. Nonspecific, concentration-dependent stimulation and repression of mammalian gene expression by small interfering RNAs (siRNAs). RNA. 2004; 10 12-18
- 110 Sledz C A, Holko M, de Veer M J et al.. Activation of the interferon system by short-interfering RNAs. Nat Cell Biol. 2003; 5 834-839
- 111 Kim D H, Longo M, Han Y et al.. Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase. Nat Biotechnol. 2004; 22 321-325
- 112 Jackson A L, Bartz S R, Schelter J et al.. Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol. 2003; 21 635-637
- 113 Hannon G J, Rossi J J. Unlocking the potential of the human genome with RNA interference. Nature. 2004; 431 371-378
- 114 Nowakowski G S, Dooner M S, Valinski H M et al.. A specific heptapeptide from a phage display peptide library homes to bone marrow and binds to primitive hematopoietic stem cells. Stem Cells. 2004; 22 1030-1038
- 115 Maitra A, Arking D E, Shivapurkar N et al.. Genomic alterations in cultured human embryonic stem cells. Nat Genet. 2005; 37 1099-1103
- 116 Solter D, Gearhart J. Putting stem cells to work. Science. 1999; 283 1468-1470
Minoru S.H KoM.D. Ph.D.
Senior Investigator and Head, Developmental Genomics & Aging Section, Laboratory of Genetics, National Institute on Aging, National Institutes of Health
333 Cassell Drive, Suite 3000, Baltimore, MD 21224-6820
Email: kom@mail.nih.gov