Consensus comparative analysis of human embryonic stem cell-derived cardiomyocytes

PLoS One. 2015 May 4;10(5):e0125442. doi: 10.1371/journal.pone.0125442. eCollection 2015.

Abstract

Global transcriptional analyses have been performed with human embryonic stem cells (hESC) derived cardiomyocytes (CMs) to identify molecules and pathways important for human CM differentiation, but variations in culture and profiling conditions have led to greatly divergent results among different studies. Consensus investigation to identify genes and gene sets enriched in multiple studies is important for revealing differential gene expression intrinsic to human CM differentiation independent of the above variables, but reliable methods of conducting such comparison are lacking. We examined differential gene expression between hESC and hESC-CMs from multiple microarray studies. For single gene analysis, we identified genes that were expressed at increased levels in hESC-CMs in seven datasets and which have not been previously highlighted. For gene set analysis, we developed a new algorithm, consensus comparative analysis (CSSCMP), capable of evaluating enrichment of gene sets from heterogeneous data sources. Based on both theoretical analysis and experimental validation, CSSCMP is more efficient and less susceptible to experimental variations than traditional methods. We applied CSSCMP to hESC-CM microarray data and revealed novel gene set enrichment (e.g., glucocorticoid stimulus), and also identified genes that might mediate this response. Our results provide important molecular information intrinsic to hESC-CM differentiation. Data and Matlab codes can be downloaded from S1 Data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cell Differentiation / genetics*
  • Computational Biology / methods
  • Databases, Nucleic Acid
  • Datasets as Topic
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Human Embryonic Stem Cells / cytology*
  • Human Embryonic Stem Cells / metabolism*
  • Humans
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism*
  • Reproducibility of Results

Grants and funding

The work described in this paper was partially supported by grants from the Research Grant Council of HKSAR [Project No. T13-706/11, HKU772913 and HKU17113514], National Natural Science Foundation of China [Project No. 61202273], Department of Education in Guangdong province [Project No. 2013KJCX0144], Construction Program of Key laboratory of Guangzhou Municipal Bureau of Science and Technology [Project No. 2014SY000022], from the funding of Outstanding Young Teachers in Higher Education Institutions of Guangdong Province [Project No. Yq201401, Guangzhou University], research project of Guangzhou Education Bureau [Project No.1201410760], and City University of Hong Kong [Project No. 7004220]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.