The mechanism of regulation by microRNA (miRNA) is complex in that miRNAs are frequently transcribed together as primary transcripts that are then processed into multiple individual mature miRNAs and, that each individual miRNA may target many different mRNAs. Thus miRNA represents a network of control over cellular functions. Additionally, the organization of many clusters of miRNAs is highly conserved and this suggests an important role for coordinated programmable function. Expression profiling of complete “microRNA-omes” enables researchers to look at this network on a broad scale and better understand the interrelationship of factors at work.
It has now been well established that miRNAs are important for the regulation of many cellular activities including cell development and differentiation. MicroRNAs play particularly important roles in human embryonic stem cells (hESC), possibly regulating self-renewal, pluripotency and differentiation. Furthermore, a better understanding of the molecular circuitry involved with reprogramming of adult cells into induced pluripotent stem cells (iPSCs) could lead to better methods of which would circumvent the need to use human embryos for research and possibly lead to the creation of disease-specific stem cells as model systems.
In a recent study, researchers at Stanford University compared the microRNA-omes of human iPSCs, hESCs, and fetal fibroblasts to unravel the regulatory networks of pluripotency and cell reprogramming . They employed LC Sciences microarray service to generate expression profiles of all known (at the time) miRNAs. Microarray data revealed the presence of a signature group of miRNAs that are upregulated in both iPSCs and hESCs vs fibroblasts as well as a cluster of miRNAs that are expressed differently in iPSCs and hESCs. The authors also note the broad changes in miRNA patterns between pluripotent cells and differentiated fibroblasts. They confirmed the expression patterns of selected miRNAs with RT-PCR.
By studying the patterns of expression as well as other factors such as the location of these clusters within genomic landscape and the functions of the genes they target, the network and the complex miRNA mechanisms can be better understood.
Wilson KD, Venkatasubrahmanyam S, Jia F, Sun N, Butte AJ, Wu JC. (2009) MicroRNA Profiling of Human-Induced Pluripotent Stem Cells. Stem Cells Dev 18, 749-758.
More information about LC Sciences miRNA profiling services is available at: http://www.lcsciences.com/mirna_discovery.html.
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