Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Defining Developmental Potency and Cell Lineage Trajectories by Expression Profiling of Differentiating Mouse ES Cells

ABSTRACT: Biologists rely on morphology, function, and specific markers to define the differentiation status of cells. Transcript profiling has expanded the repertoire of these markers by providing the snapshot of cellular status that reflects the activity of all genes. However, such data have been used only to assess relative similarities and differences of these cells. Here we show that principal component analysis (PCA) of global gene expression profiles map cells in multidimensional transcript profile space and the positions of differentiating cells progress in a stepwise manner along trajectories starting from undifferentiated embryonic stem (ES) cells located in the apex. We present three cell lineage trajectories, which represent the differentiation of ES cells into the first three lineages in mammalian development: primitive endoderm, trophoblast, and primitive ectoderm/neural ectoderm. The positions of the cells along these trajectories seem to reflect the developmental potency of cells and can be used as a scale for the potential of cells. Indeed, we show that embryonic germ (EG) cells and induced pluripotent (iPS) cells are mapped near the origin of the trajectories, whereas mouse embryo fibroblast (MEF) and fibroblast cell lines are mapped near the far end of the trajectories. We propose that this method can be used as the non-operational semi-quantitative definition of cell differentiation status and developmental potency. Furthermore, the global expression profiles of cell lineages provide a framework for the future study of in vitro and in vivo cell differentiation. Keywords: cell type comparison design,reference design,replicate design,time series design Most of the cells and RNA samples used in this study were described in detail previously (See paper's citation associated with this dataset). To maximize the uniformity of the microarray data, all the samples, including ones analyzed by DNA microarray previously, were hybridized to the same platform (the NIA Mouse 44K Microarray manufactured by Agilent Technologies: AMADID #015087). The intensity of each gene feature per array was extracted from scanned microarray images using Feature Extraction Software V9.5.

ORGANISM(S): Mus musculus

SUBMITTER: Minoru Ko

PROVIDER: E-GEOD-11523 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Defining developmental potency and cell lineage trajectories by expression profiling of differentiating mouse embryonic stem cells.

Aiba Kazuhiro K Nedorezov Timur T Piao Yulan Y Nishiyama Akira A Matoba Ryo R Sharova Lioudmila V LV Sharov Alexei A AA Yamanaka Shinya S Niwa Hitoshi H Ko Minoru S H MS

DNA research : an international journal for rapid publication of reports on genes and genomes 20081226 1

Biologists rely on morphology, function and specific markers to define the differentiation status of cells. Transcript profiling has expanded the repertoire of these markers by providing the snapshot of cellular status that reflects the activity of all genes. However, such data have been used only to assess relative similarities and differences of these cells. Here we show that principal component analysis of global gene expression profiles map cells in multidimensional transcript profile space ...[more]

PMID: 19112179

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Project description:Degradation of mRNA is one of the key processes that control the steady-state level of gene expression. However, the rate of mRNA decay for the majority of genes is not known. We successfully obtained the rate of mRNA decay for 19 977 non-redundant genes by microarray analysis of RNA samples obtained from mouse embryonic stem (ES) cells. Median estimated half-life was 7.1 h and only <100 genes, including Prdm1, Myc, Gadd45 g, Foxa2, Hes5 and Trib1, showed half-life less than 1 h. In general, mRNA species with short half-life were enriched among genes with regulatory functions (transcription factors), whereas mRNA species with long half-life were enriched among genes related to metabolism and structure (extracellular matrix, cytoskeleton). The stability of mRNAs correlated more significantly with the structural features of genes than the function of genes: mRNA stability showed the most significant positive correlation with the number of exon junctions per open reading frame length, and negative correlation with the presence of PUF-binding motifs and AU-rich elements in 30 -untranslated region (UTR) and CpG di-nucleotides in the 50 -UTR. The mRNA decay rates presented in this report are the largest data set for mammals and the first for ES cells. Keywords: growth condition design,reference design,replicate design,RNA stability design,time series design We used two mouse ESC lines: MC1 derived from mouse strain 129S6/SvEvTac and MC2-B6 derived from strain C57BL/6J. To remove contaminating feeder cells, ES cells were first cultured for two passages on gelatin-coated culture dish in complete ES medium. Differentiated ES cells were obtained from MC1 cells by LIF withdrawal (complete medium without LIF, below referenced as LIF-) or by retinoic acid (RA) treatment. To measure mRNA stability, transcription was blocked by adding actinomycin D to the medium. RNA was hybridized in duplicate for each cell type and time point. All hybridizations were carried out by combining a Cy3-CTP-labeled experimental target and a Cy5-CTP-labeled Universal Mouse Reference target.

Dataset Information

Defining Developmental Potency and Cell Lineage Trajectories by Expression Profiling of Differentiating Mouse ES Cells

Publications

Defining developmental potency and cell lineage trajectories by expression profiling of differentiating mouse embryonic stem cells.

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