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Title: Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4 alpha
Authors: Koh, W
Sheng, C.T
Tan, B
Lee, Q.Y
Kuznetsov, V
Kiang, L.S 
Tanavde, V
Keywords: hepatic nuclear factor 4 alpha
nucleic acid binding protein
unclassified drug
hepatocyte nuclear factor 4
HNF4A protein, human
mirnlet7 microRNA, human
cell cycle regulation
cell differentiation
cell renewal
controlled study
embryonic stem cell
gene expression profiling
gene function
gene interaction
gene sequence
genetic analysis
genetic association
human cell
mesenchymal stem cell
sequence alignment
signal transduction
cell culture
cell lineage
gene expression profiling
gene regulatory network
genetic transcription
nucleotide sequence
Base Sequence
Cell Lineage
Cells, Cultured
Embryonic Stem Cells
Gene Expression Profiling
Gene Regulatory Networks
Hepatocyte Nuclear Factor 4
Mesenchymal Stem Cells
Transcription, Genetic
Issue Date: 2010
Citation: Koh, W, Sheng, C.T, Tan, B, Lee, Q.Y, Kuznetsov, V, Kiang, L.S, Tanavde, V (2010). Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4 alpha. BMC Genomics 11 (SUPPL. 1) : S6. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Background: Recent literature has revealed that genetic exchange of microRNA between cells can be essential for cell-cell communication, tissue-specificity and developmental processes. In stem cells, as in other cells, this can be accomplished through microvesicles or exosome mediated transfer. However, molecular profiles and functions of microRNAs within the cells and in their exosomes are poorly studied. Next generation sequencing technologies could provide a broad-spectrum of microRNAs and their expression and identify possible microRNA targets. In this work, we performed deep sequencing of microRNAs to understand the profile and expression of the microRNAs in microvesicles and intracellular environment of human embryonic stem cells derived mesenchymal stem cells (hES-MSC).We outline a workflow pertaining to visualizing, statistical analysis and interpreting deep sequencing data of known intracellular and extracellular microRNAs from hES-MSC). We utilized these results of which directed our attention towards establishing hepatic nuclear factor 4 alpha (HNF4A) as a downstream target of let-7 family of microRNAs.Results: In our study, significant differences in expression profile of microRNAs were found in the intracellular and extracellular environment of hES-MSC. However, a high level of let-7 family of microRNAs is predominant in both intra- and extra- cellular samples of hES-MSC. Further results derived from visualization of our alignment data and network analysis showed that let-7 family microRNAs could affect the downstream target HNF4A, which is a known endodermal differentiation marker. The elevated presence of let-7 microRNA in both intracellular and extra cellular environment further suggests a possible intercellular signalling mechanism through microvesicles transfer. We suggest that let-7 family microRNAs might play a signalling role via such a mechanism amongst populations of stem cells in maintaining self renewal property by suppressing HNF4A expression. This is in line with recent paradigm where microRNAs regulate self-renewal and differentiation pathways of embryonic stem cells by forming an integral biological network with transcription factors.Conclusion: In summary, our study using a combination of alignment, statistical and network analysis tools to examine deep sequencing data of microRNAs in hES-MSC has led to a result that (i) identifies intracellular and exosome microRNA expression profiles of hES-MSCwith a possible mechanism of miRNA mediated intercellular regulation by these cells and (ii) placed HNF4A within the cross roads of regulation by the let-7 family of microRNAs. © 2010 Koh et al; licensee BioMed Central Ltd.
Source Title: BMC Genomics
ISSN: 14712164
DOI: 10.1186/1471-2164-11-S1-S6
Rights: Attribution 4.0 International
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