A mRNA landscape of bovine embryos after standard and MAPK-inhibited culture conditions: a comparative analysis

BMC Genomics

Bernard AJ Roelen⁵  Henk P Haagsman³  Kaveh Mashayekhi²  Sascha G IJzer⁵  Frank M Riemers⁴  Marian JA Groot Koerkamp¹  Helena TA van Tol⁵  Bas Brinkhof⁵ 

[1] University Medical Center Utrecht, Molecular Cancer Research, Utrecht 3508 AB, The Netherlands;BioTalentum Ltd, Aulich L u.26, Gödöllő 2100, Hungary;Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, Utrecht 3584 CL, The Netherlands;Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, University Utrecht, Yalelaan 108, Utrecht 3584 CM, The Netherlands;Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, Utrecht 3584 CM, The Netherlands

关键词: MAPK;    NANOG;    Trophectoderm;    ICM;    Blastocyst;    Morula;    Cattle;    Pluripotency;   

Others  :  1170981
DOI  :  10.1186/s12864-015-1448-x

 received in 2015-02-26, accepted in 2015-03-06,  发布年份 2015

【 摘 要 】

Background

Genes and signalling pathways involved in pluripotency have been studied extensively in mouse and human pre-implantation embryos and embryonic stem (ES) cells. The unsuccessful attempts to generate ES cell lines from other species including cattle suggests that other genes and pathways are involved in maintaining pluripotency in these species. To investigate which genes are involved in bovine pluripotency, expression profiles were generated from morula, blastocyst, trophectoderm and inner cell mass (ICM) samples using microarray analysis. As MAPK inhibition can increase the NANOG/GATA6 ratio in the inner cell mass, additionally blastocysts were cultured in the presence of a MAPK inhibitor and changes in gene expression in the inner cell mass were analysed.

Results

Between morula and blastocyst 3,774 genes were differentially expressed and the largest differences were found in blastocyst up-regulated genes. Gene ontology (GO) analysis shows lipid metabolic process as the term most enriched with genes expressed at higher levels in blastocysts. Genes with higher expression levels in morulae were enriched in the RNA processing GO term. Of the 497 differentially expressed genes comparing ICM and TE, the expression of NANOG, SOX2 and POU5F1 was increased in the ICM confirming their evolutionary preserved role in pluripotency. Several genes implicated to be involved in differentiation or fate determination were also expressed at higher levels in the ICM. Genes expressed at higher levels in the ICM were enriched in the RNA splicing and regulation of gene expression GO term. Although NANOG expression was elevated upon MAPK inhibition, SOX2 and POU5F1 expression showed little increase. Expression of other genes in the MAPK pathway including DUSP4 and SPRY4, or influenced by MAPK inhibition such as IFNT, was down-regulated.

Conclusion

The data obtained from the microarray studies provide further insight in gene expression during bovine embryonic development. They show an expression profile in pluripotent cells that indicates a pluripotent, epiblast-like state. The inability to culture ICM cells as stem cells in the presence of an inhibitor of MAPK activity together with the reported data indicates that MAPK inhibition alone is not sufficient to maintain a pluripotent character in bovine cells.

【 授权许可】

   
2015 Brinkhof et al.; licensee BioMed Central.

【 图 表 】

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