Network based meta-analysis prediction of microenvironmental relays involved in stemness of human embryonic stem cells
A peer-reviewed article of this Preprint also exists.
Author and article information
Abstract
Background. Human embryonic stem cells (hESCs) are pluripotent cells derived from the inner cell mass of in vitro fertilised blastocysts, which can either be maintained in an undifferentiated state or committed into lineages under determined culture conditions. These cells offer great potential for regenerative medicine, but at present, little is known about the mechanisms that regulate hESC stemness; in particular, the role of cell-cell and cell-extracellular matrix interactions remain relatively unexplored. Methods and results. In this study we have performed an in silico analysis of cell-microenvironment interactions to identify novel proteins that may be responsible for the maintenance of hESC stemness. A hESC transcriptome of 8,934 mRNAs was assembled using a meta-analysis approach combining the analysis of microarrays and the use of databases for annotation. The STRING database was utilised to construct a protein-protein interaction network focused on extracellular and transcription factor components contained within the assembled transcriptome. This interactome was structurally studied and filtered to identify a short list of 92 candidate proteins, which may regulate hESC stemness. Conclusion. We hypothesise that this list of proteins, either connecting extracellular components with transcriptional networks, or with hub or bottleneck properties, may contain proteins likely to be involved in determining stemness.
Cite this as
2014. Network based meta-analysis prediction of microenvironmental relays involved in stemness of human embryonic stem cells. PeerJ PrePrints 2:e415v2 https://doi.org/10.7287/peerj.preprints.415v2note This preprint is not peer-reviewed. You may wish to reference the subsequent peer-reviewed version of this article.
Author comment
This is an update of a previous version based on reviewers' comments.
Sections
Supplemental Information
The hESC putative interactomes
The hESC EC+TF putative interactomes A) ALL and B) C+S (C: common part; S: specific part). (Cytoscape file)
List of mRNAs forming hESC and hESC-derived transcriptomes
Each mRNA is identified by the EntrezGene ID, the Official Gene Symbol and the full gene name. 'Transcriptome' column: transcriptome(s) or sub-transcriptome containing the mRNAs (hESC: human embryonic stem cells; Endo: endothelial cell; F: fibroblast; Mix: mixture of hESC-derived cells). Colour code (see Legend sheet) indicates different transcriptome and sub-transcriptomes. GO term column: GO terms found during the GO extraction (CA: cell adhesion; CC: cell cycle; CCo: cell communication; CS: cytoskeleton organisation; J: cell junction; EC: extracellular part; HS: heparan sulfate binding proteins; TF: transcription factor related part). (Excel file)
General network parameters
ALL R is the randomised network from the ALL interactome while C+S R is the randomised network from the C+S interactome (C: common part; S: specific part; R: random). Power law of the degree distribution: <!--[if !msEquation]--> <!--[endif]--> with R2, the polynomial regression coefficient (degree 2).
GO/KEGG analyses
GO Biological Processes term and KEGG pathway enrichments analysis of A) EC+TF interactomes, B) full lists of candidates and C-I) sub-sets of candidates (EC: extracellular part; TF: transcription factor related part).
The complete list of candidates
Each protein is identified by its corresponding EntrezGene ID, gene acronym and full gene name. 'Transcriptome' column: transcriptome(s) or sub-transcriptome containing the corresponding mRNA (Endo: endothelial cell; F: fibroblast; Mix: mixture of hESC-derived cells). A colour code is applied to aid recognition of each transcriptome and sub-transcriptome (see the Legend sheet). GO term column: GO terms found during the GO term analysis (CA: cell adhesion; CC: cell cycle; CCo: cell communication; CS: cytoskeleton; J: cell junction; EC: extracellular part; HS: heparan sulfate binding proteins; TF: transcription factor related part). "Hubs" column: indicates the number of edges associated with each hub protein. 'S/C' and 'EC/TF' columns: indicates if a protein is in the specific/common interface or extracellular/transcription factor interface respectively. A) the longest ALL_EC+TF list of candidates, B) the random list, C) the ALL_EC list, D) the C+S_EC+TF list and E) the shortest C+S_EC list of candidate proteins, in which C = common part and S = specific part. (Excel file)
Additional Information
Competing Interests
We declare no competing interests.
Author Contributions
Virginie Mournetas conceived and designed the experiments, performed the experiments, analyzed the data, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Quentin M. Nunes conceived and designed the experiments, contributed reagents/materials/analysis tools, wrote the paper, reviewed drafts of the paper.
Patricia A. Murray conceived and designed the experiments, wrote the paper, reviewed drafts of the paper.
Christopher M. Sanderson conceived and designed the experiments, wrote the paper, reviewed drafts of the paper.
David G. Fernig conceived and designed the experiments, wrote the paper, reviewed drafts of the paper.
Funding
This work was partly funded by North West Cancer Research and BBSRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
