Transcriptome Analysis of Mouse Stem Cells and Early Embryos

Sharov, Alexei A.; Piao, Yulan; Matoba, Ryo; Dudekula, Dawood B.; Qian, Yong; VanBuren, Vincent; Falco, Geppino; Martin, Patrick R.; Stagg, Carole A.; Bassey, Uwem C.; Wang, Yuxia; Carter, Mark G.; Hamatani, Toshio; Aiba, Keisuke; Akutsu, Hidenori; Sharova, Lioudmila V.; Tanaka, Tetsuya; Kimber, Wendy L.; Yoshikawa, Toshiyuki; Jaradat, Saied; Pantano, Serafino; Nagaraja, Ramaiah; Boheler, Kenneth R.; Taub, Dennis D.; Hodes, Richard J.; Longo, Dan L.; Schlessinger, David; Keller, Jonathan R.; Klotz, Emily; Kelsoe, Garnett; Umezawa, Akihiro; Vescovi, Angelo L.; Rossant, Janet; Kunath, Tilo; Hogan, Brigid L.M.; Curci, Anna; D’Urso, Michele; Kelso, Janet; Hide, Winston; Ko, Minoru S.H.

doi:10.1371/journal.pbio.0000074

Cited by 164 publications

(60 citation statements)

References 40 publications

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“…For proper developmental outcome, ESCs must tightly regulate their differentiation status, and through continuing study, the molecular basis of that regulation process is beginning to emerge. Systematic, genome-wide interrogations have identified hundreds of genes, including several transcription factors, which have expression patterns tightly correlated with ES cell differentiation (1)(2)(3)(4)(5)(6). Two key transcription factors, Oct4 and Sox2, have been identified that are crucial for maintenance of the pluripotent state of ESCs (7,8).…”

Section: Embryonic Stem Cells (Escs)mentioning

confidence: 99%

Oct4 and Sox2 Directly Regulate Expression of Another Pluripotency Transcription Factor, Zfp206, in Embryonic Stem Cells

Wang

Teh

Kueh

et al. 2007

Journal of Biological Chemistry

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It is well known that Oct4 and Sox2 play an important role in the maintenance of embryonic stem cell pluripotency. These transcription factors bind to regulatory regions within hundreds of target genes to control their expression. Zfp206 is a recently characterized transcription factor that has a role in maintaining stem cell pluripotency. We have demonstrated here that Zfp206 is a direct downstream target of Oct4 and Sox2. Two composite sox-oct binding sites have been identified within the first intron of Zfp206. We have demonstrated binding of Oct4 and Sox2 to this region. In addition, we have shown that Oct4 or Sox2 alone can activate transcription via one of these sox-oct elements, although the presence of both Oct4 and Sox2 gave rise to a synergistic effect. These studies extend our understanding of the transcriptional network that operates to regulate the differentiation potential of embryonic stem cells. Embryonic stem cells (ESCs)2 are derived from the inner cell mass of the blastocyst and exhibit both pluripotency and selfrenewing capabilities. For proper developmental outcome, ESCs must tightly regulate their differentiation status, and through continuing study, the molecular basis of that regulation process is beginning to emerge. Systematic, genome-wide interrogations have identified hundreds of genes, including several transcription factors, which have expression patterns tightly correlated with ES cell differentiation (1-6). Two key transcription factors, Oct4 and Sox2, have been identified that are crucial for maintenance of the pluripotent state of ESCs (7,8). ESCs lose the capacity to maintain pluripotency upon knockdown of expression of these transcription factors by RNA interference (9, 10). Gene knock-out studies confirm the importance of Oct4 and Sox2 for early embryonic development. It has been demonstrated by chromatin immunoprecipitation studies that Oct4 and Sox2 bind to a few thousand regulatory sites in the ES cell genome (11,12). It is likely that many of these target genes play a role in modulating ES cell differentiation. Indeed, the transcription factor Nanog, an established regulator of pluripotency, is transcriptionally regulated directly by Oct4 and Sox2 (13).Zfp206 is a transcription factor that is highly expressed in mouse and human ESCs and down-regulated upon differentiation (3, 14). Zfp206 contains a SCAN domain and 14 zinc-finger domains, which suggests that it may be a transcription factor that binds DNA directly. Zfp206 is expressed in the inner cell mass but not in trophectoderm, suggesting that it may play a role in establishing cell fate decisions regarding embryonic versus extraembryonic tissue (15). There is wide temporal and spatial distribution of RNA and protein in the early embryos, indicating that Zfp206 may regulate multiple cell fate decisions (14). Recent data have demonstrated that overexpression of Zfp206 promotes the formation of undifferentiated mouse ESC colonies in vitro (14). We have obtained similar results and further found that overexpression of Zf...

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Section: Embryonic Stem Cells (Escs)mentioning

confidence: 99%

Oct4 and Sox2 Directly Regulate Expression of Another Pluripotency Transcription Factor, Zfp206, in Embryonic Stem Cells

Wang

Teh

Kueh

et al. 2007

Journal of Biological Chemistry

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“…Until recently, quantitative analysis of high-resolution, two-dimensional protein gels (Latham et al 1991), mRNA differential display (Ma et al 2001), analysis of expressed sequence tags derived from libraries of various preimplantation stages (Ko et al 2000, Sharov et al 2003 and analysis of selected genes (Ho et al 1995) have been used. Although these approaches have shed some light on the molecular basis underlying preimplantation development, they offer limited insight because only a small number of genes can be readily analyzed.…”

Section: Introductionmentioning

confidence: 99%

Effects of embryo culture on global pattern of gene expression in preimplantation mouse embryos

Rinaudo

Schultz²

2004

Reproduction

237

176

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Culture of preimplantation embryos affects gene expression. The magnitude of the effect on the global pattern of gene expression, however, is not known. We compared global patterns of gene expression in blastocysts cultured from the one-cell stage in either Whitten's medium or KSOM 1 amino acids (KSOM/AA) with that of blastocysts that developed in vivo, using the Affymetrix MOE430A chip. The analysis revealed that expression of 114 genes was affected after culture in Whitten's medium, whereas only 29 genes were mis-expressed after culture in KSOM/AA. Expression Analysis Systematic Explorer was used to identify biological and molecular processes that are perturbed after culture and indicated that genes involved in protein synthesis, cell proliferation and transporter function were down-regulated after culture in Whitten's medium. A common set of genes involved in transporter function was also down-regulated after culture in KSOM/AA. These results provide insights as to why embryos develop better in KSOM/AA than in Whitten's medium, and highlight the power of microarray analysis to assess global patterns of gene expression.

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“…Recently, Cdk2ap1 has been identified as one of the stem cell-specific genes that are enriched in both embryonic and adult stem cells (16). Cdk2ap1 has been categorized as one of genes that are expressed in early stage preimplantation embryos (17). In addition, Cdk2ap1 mRNA has been found to be elevated upon estrogen treatment during early implantation process, suggesting its role in uterine decidualization (18).…”

mentioning

confidence: 99%

Cyclin-dependent Kinase 2-associating Protein 1 Commits Murine Embryonic Stem Cell Differentiation through Retinoblastoma Protein Regulation

Kim¹,

Deshpande²,

Dai³

et al. 2009

Journal of Biological Chemistry

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Mouse embryonic stem cells (mESCs) maintain pluripotency and indefinite self-renewal through yet to be defined molecular mechanisms. Leukemia inhibitory factor has been utilized to maintain the symmetrical self-renewal and pluripotency of mESCs in culture. It has been suggested that molecules with significant cellular effects on retinoblastoma protein (pRb) or its related pathways should have functional impact on mESC proliferation and differentiation. However, the involvement of pRb in pluripotent differentiation of mESCs has not been extensively elaborated. In this paper, we present novel experimental data indicating that Cdk2ap1 (cyclin-dependent kinase 2-associating protein 1), an inhibitor of G 1 /S transition through down-regulation of CDK2 and an essential gene for early embryonic development, confers competency for mESC differentiation. Targeted disruption of Cdk2ap1 in mESCs resulted in abrogation of leukemia inhibitory factor withdrawalinduced differentiation, along with altered pRb phosphorylation. The differentiation competency of the Cdk2ap1 ؊/؊ mESCs was restored upon the ectopic expression of Cdk2ap1 or a nonphosphorylatable pRb mutant (mouse Ser 788 3 Ala), suggesting that the CDK2AP1-mediated differentiation of mESCs was elicited through the regulation of pRb. Further analysis on mESC maintenance or differentiation-related gene expression supports the phosphorylation at serine 788 in pRb plays a significant role for the CDK2AP1-mediated differentiation of mESCs. These data clearly demonstrate that CDK2AP1 is a competency factor in the proper differentiation of mESCs by modulating the phosphorylation level of pRb. This sheds light on the role of the establishment of the proper somatic cell type cell cycle regulation for mESCs to enter into the differentiation process.

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Transcriptome Analysis of Mouse Stem Cells and Early Embryos

Cited by 164 publications

References 40 publications

Oct4 and Sox2 Directly Regulate Expression of Another Pluripotency Transcription Factor, Zfp206, in Embryonic Stem Cells

Oct4 and Sox2 Directly Regulate Expression of Another Pluripotency Transcription Factor, Zfp206, in Embryonic Stem Cells

Effects of embryo culture on global pattern of gene expression in preimplantation mouse embryos

Cyclin-dependent Kinase 2-associating Protein 1 Commits Murine Embryonic Stem Cell Differentiation through Retinoblastoma Protein Regulation

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