Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10940182 | Gene Expression Patterns | 2014 | 15 Pages |
Abstract
The differentiation to cardiomyocytes is a prerequisite and an important part of heart development. A good understanding of the complicated cardiomyocyte differentiation process benefits cardiogenesis study. Embryonic stem cells (ESCs), cell lines with infinite ability to proliferate and to be differentiated into all cell types of the adult body, are important research tools for investigation of differentiation and meanwhile good models for developmental research. In the current study, genome-wide gene expression of ESCs is profiled through high throughput platform during cardiomyocyte-specific differentiation and maturation. Gene expression patterns of undifferentiated ESCs and ESC-derived cardiomyocytes provide a global overview of genes involved in cardiomyocyte-specific differentiation, whereas marker gene expression profiles of both ESC-related genes and cardiac-specific genes presented the expression pattern shift during differentiation in a pure ESC-derived cardiomyocyte cell culture system. The differentiation and maturation process was completed at day 19 after initiation of differentiation, according to our gene expression profile results. Functional analysis of regulated genes reveals over-represented biological processes, molecular functions and pathways during the differentiation and maturation process. Finally, transcription factor regulation networks were engineered based on gene expression data. Within these networks, the number of identified important regulators (Trim28, E2f4, Foxm1, Myc, Hdac1, Rara, Mef2c, Nkx2-5, Gata4) and possible key co-regulation modules (Nkx2-5 - Gata4 - Tbx5, Myc - E2F4) could be expanded. We demonstrate that a more comprehensive picture of cardiomyocyte differentiation and its regulation can be achieved solely by studying gene expression patterns. The results from our study contribute to a better and more accurate understanding of the regulation mechanisms during cardiomyocyte differentiation.
Keywords
FCSKEGGtranscription factor regulationMurine embryonic stem cellsα-MHCIMDMDMEMeGFPDulbecco's modified Eagle's mediumIscove's modified Dulbecco's mediumPCAchromatin immunoprecipitationMolecular functionPrincipal component analysisCardiomyocyte differentiationRegulation networkHeart developmentembryoid bodiesESCKyoto Encyclopedia of Genes and Genomesα-Myosin heavy chainfetal calf serumEmbryonic stem cellsTranscription factorsbiological processGene ontologyenhanced green fluorescence proteinTranscriptome profilingCHiP
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cell Biology
Authors
Lin Gan, Silke Schwengberg, Bernd Denecke,