A review of gene expression profiling of human embryonic stem cell lines and their differentiated progeny

Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Current Stem Cell Research & Therapy (Impact Factor: 2.86). 06/2009; 4(2):98-106. DOI: 10.2174/157488809788167409
Source: PubMed

ABSTRACT One of the key characteristics of human embryonic stem cells (hESC) is their ability to proliferate for an indefinite period of time. Previous studies have shown that a unique network of transcription factors are involved in hESC self renewal. Since hESC lines have the potential to differentiate into cells of all three germ layers, cells derived from hESC may be useful for the treatment of a variety of inherited or acquired diseases. The molecular signal required to differentiate hESC into a particular cell type has not been defined. It is expected that global gene expression profiling of hESC may provide an insight into the critical genes involved in maintaining pluripotency of hESC and genes that are modulated when hESCs differentiate. Several groups have utilized a variety of high throughput techniques and performed gene expression profiling of undifferentiated hESCs and mouse ES cells (mESC) to identify a set of genes uniquely expressed in ES cells but not in mature cells and defined them as "stemness" genes. These molecular techniques include DNA microarray, EST-enumeration, MPSS profiling, and SAGE. Irrespective of the molecular technique used, highly expressed genes showed similar expression pattern in several ES cell lines supporting their importance. A set of approximately 100 genes were identified, which are highly expressed in ES cells and considered to be involved in maintaining pluripotency and self renewal of ES cells. Various studies have also reported on the gene expression profiling of differentiated embryoid bodies (EB) derived from hESCs and mESCs. When hESCs are differentiated, "stemness" genes are down-regulated and a set of genes are up-regulated. Together with down-modulation of "stemness" genes and up-regulation of new genes may provide a new insight into the molecular pathways of hESC differentiation and study of these genes may be useful in the characterization of differentiated cells.

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    • "Since a considerable number of the predicted genes by promoter analysis were not upregulated based on the microarray data , we assumed that they might be repressed during hESC growth or could be due to species differences or culture condition ( Bhattacharya et al . , 2009 ) . Therefore the second PI network was constructed using the all 328 predicted genes by promoter analysis ( Supplementary material 4 ) . Three hundred and two out of 328 genes could be predicted in the network . Interestingly , 126 of the predicted downregulated genes were present in the network ( Supplementary material 5 ) . Fig . 2 r"
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    ABSTRACT: Self-proliferation and differentiation into distinct cell types have been made stem cell as a promising target for regenerative medicine. Several key genes can regulate self-renewal and pluripotency of embryonic stem cells (hESCs). They work together and build a transcriptional hierarchy. Coexpression and coregulation of genes control by common regulatory elements on the promoter regions. Consequently, distinct organization and combination of transcription factor binding sites (TFBSs modules) on promoter regions, in view of order and distance, leads to a common specific expression pattern within a set of genes. To gain insights into transcriptional regulation of hESCs, we selected promoter regions of eleven common expressed hESC genes including SOX2, LIN28, STAT3, NANOG, LEFTB, TDGF1, POU5F1, FOXD3, TERF1, REX1 and GDF3 to predict activating regulatory modules on promoters and discover key corresponding transcription factors. Then, promoter regions in human genome were explored for modules and 328 genes containing the same modules were detected. Using microarray data, we verified that 102 of 328 genes commonly upregulate in hESCs. Also, using output data of DNA-Protein interaction assays, we found that 42 of all predicted genes are targets of SOX2, NANOG and POU5F1 . Additionally, a protein interaction network of hESC genes was constructed based on biological processes and interestingly, 126 downregulated genes along with upregulated ones identified by promoter analysis were predicted in the network. Based on the results, we suggest that the identified genes, coregulating with common hESC genes, represent a novel approach for gene discovery based on whole genome promoter analysis irrespective of gene expression. Altogether, promoter profiling can be used to expand hESC transcriptional regulatory circuitry by analysis of shared functional sequences between genes. This approach provides a clear image on underlying regulatory mechanism of gene expression profile and offers a novel approach in designing gene networks of stem cell.
    Gene 09/2013; 531(2). DOI:10.1016/j.gene.2013.09.011 · 2.08 Impact Factor
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    • "Continued progress toward realizing the potential of human pluripotent stem cells will be facilitated by robust datasets and complementary resources that are easily accessed and interrogated by the stem cell community. Many genome-wide microarray expression studies have been performed on hESCs using a variety of different technologies (Bock et al., 2011; Chin et al., 2009; Liu et al., 2006; Muller et al., 2011; Rao et al., 2004; Skottman et al., 2005; Sperger et al., 2003 and reviewed in Bhattacharya et al., 2009). To complement the existing data, we report here the establishment of the Human Pluripotent Stem Cell Database at the National Institutes of Health (NIH), StemCellDB, where we provide an in-house dataset of pluripotent human stem cells. "
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    ABSTRACT: Much of the excitement generated by induced pluripotent stem cell technology is concerned with the possibility of disease modeling as well as the potential for personalized cell therapy. However, to pursue this it is important to understand the 'normal' pluripotent state including its inherent variability. We have performed various molecular profiling assays for 21 hESC lines and 8 hiPSC lines to generate a comprehensive snapshot of the undifferentiated state of pluripotent stem cells. Analysis of the gene expression data revealed no iPSC-specific gene expression pattern in accordance with previous reports. We further compared cells, differentiated as embryoid bodies in 2 media proposed to initiate differentiation towards separate cell fates, as well as 20 adult tissues. From this analysis we have generated a gene list which defines pluripotency and establishes a baseline for the pluripotent state. Finally, we provide lists of genes enriched under both differentiation conditions which show the proposed bias toward independent cell fates.
    Stem Cell Research 09/2012; 10(1):57-66. DOI:10.1016/j.scr.2012.09.002 · 3.91 Impact Factor
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    • "hPSCs are functionally defined by their self-renewal and differentiation potential. They can be induced to differentiate in vitro into virtually all human cell types (Bhattacharya et al., 2009). A diseased or injured central nervous system (CNS) has little capacity to compensate for the loss of cellular elements (neurons , oligodendrocytes; Barrett et al., 2007), thus, cell replacement is an interesting prospective [i.e., missing dopaminergic neurons in Parkinson's diseased brain; missing motoneurons in amyotrophic lateral sclerosis (ALS) or spinal cord injury]. "
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    ABSTRACT: Human pluripotent stem cells (hPSCs) represent a new and exciting field in modern medicine, now the focus of many researchers and media outlets. The hype is well-earned because of the potential of stem cells to contribute to disease modeling, drug screening, and even therapeutic approaches. In this review, we focus first on neural differentiation of these cells. In a second part we compare the various cell types available and their advantages for in vitro modeling. Then we provide a "state-of-the-art" report about two major biomedical applications: (1) the drug and toxicity screening and (2) the neural tissue replacement. Finally, we made an overview about current biomedical research using differentiated hPSCs.
    Frontiers in Physiology 03/2012; 3:47. DOI:10.3389/fphys.2012.00047 · 3.50 Impact Factor
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