The miRNAomc of the Immortal Planaria, Schmidtea mediterranea, and Insights on the Molecular Evolution of Pluripotency in Human Embryonic Stem Cells

Abstract

The evolution of the ability of planarians such as Schmidtea mediterranea to regenerate organs and tissues through neoblasts has interested biologists for a long time. This study determined if there were genes that had been lost in the molecular evolution of pluripotency genes from planarians to humans. Utilizing miRBase and a study by Palakodeti, et al. (2006) as reference, 9 miRNAs were found to be conserved in humans. Two of these miRNAs have potential targets related to pluripotency: sme-let-7a and sme-mir-190b. Comparative miRnomics of the 2 miRNAs with miRNAs found in human embryonic stem cells was conducted and the results were compared to microarray data from Cao, et al. (2008). Two planarian miRNAs, let-7a and mir-190b that were conserved in humans v/ere (bund partially homologous to 8 hESC miRNAs that target pluripotency genes: hsa-mir-299, hsa-Iet-7a, hsa-mir-21, hsa-mir-374a, hsa-mir- 367, hsa-mir-16-2, hsa-mir-154, and hsa-mir-369. In the same study, only 2 miRNAs, hsa-mir-367 and hsa-let-7a, were reported to have been up-and down- regulated, respectively. Hsa-inir-367 has KLF4, NANOG, and LIN28 as its potential targets. Since this niiRNA was found to be up-regulated, its target genes will most likely be inhibited. Hsa-let-7a was the most down-regulated miRNA, indicating that its potential targets, MYC and LIN28, and the gene it was partially homologous with, KLF4, would be expressed. Of the 9 planarian miRNAs conserved in humans, only one was down-regulated in hESCs. Due to low homology score (20%), it was suggested that hsa-let-7a could have been modified and is no longer functionally related to sme-let-7a. Therefore, humans are not capable of regenerating major body parts because the pluripotency genes that can give hurnans the ability to regenerate major body parts like the Schmidtea mediterranea were not expressed.