miRNA
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In 1963, Becker, McCulloch, and Till presented the first evidence of the utility of stem cells in Nature with the paper "Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells". Since that time, stem cell research has opened new doors of promise for regerative medicine, while moving to the forefront of political controversy. In spite of the controversy, a number of experimental stem cell treatments have already been developed, though not frequently applied due to their unvalidated nature and cost-limitations. Many in the medical community believe that stem cells hold the key to treating cancer, spinal cord injuries, and muscle damage, as well as a number of other diseases and impairments. There has been significant research thus far, from temporal changes in development to the epigenetic mechanisms that define stem cell differentiation. New attention to miRNAs and the regulatory role that they play in gene expression have resulted in increased interest in their possible role in tissue morphogenesis and cell differentiation. Recent studies have demonstrated the importance of miRNAs in embryonic stem cell differentiation, limb development, adipogenesis, myogenesis, angiogenesis and hematopoiesis, neurogenesis, and epithelial morphogenesis. Traditionally, miRNA expression has been tested using low-throughput techniques such as Northern-blot analysis and real-time PCR, but new developments in microarray technology now enable global profiling of all miRNA genes and their precursors in any sample type.
Krichevsky and colleagues (2006) examined the modulation of embryonic stem cell-derived neurogenesis through miRNA interactions. The group used miRNA expression profiling in mouse embryonic stem (ES) cell– derived neurogenesis in vitro to show that a number of miRNAs were simultaneously co-induced during differentiation of neural progenitor cells to neurons and astrocytes. The researchers found a clear correlation between miRNA expression profiles in ES cell– derived neurogenesis in vitro and in embryonal neurogenesis in vivo. Using both gain-of-function and loss-of-function approaches, they demonstrated that brain-specific miR-124a and miR-9 molecules affected neural lineage differentiation in the ES cell– derived cultures. In addition, they provided evidence that signal transducer and activator of transcription (STAT) 3, a member of the STAT family pathway, was involved in the function of these miRNAs. The results of this study implicate distinct miRNAs as possessing a functional role in the determination of neural fates in ES cell differentiation.
Title: Specific microRNAs modulate embryonic stem cell-derived neurogenesis.
Authors: Krichevsky AM, Sonntag KC, Isacson O, Kosik KS
Journal: Stem Cells, Vol 24, Issue 4: 857-64
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In a collaborative effort, S. D. Hatfield, H. R. Shcherbata, and other researchers elucidated the necessity of the microRNA (miRNA) pathway for proper control of germline stem cell (GSC) division in Drosophila melanogaster. In order to determine the role of miRNAs in the control of stem cell biology, the researchers specifically eliminated processing of all miRNAs in stem cells through impaired Dicer-1 activity (the enzyme essential for processing miRNAs) in Drosophila germline stem cells (GSCs). Results indicated that miRNAs were required for GSCs to transit the G1/S checkpoint by repressing directly or indirectly the G1/S inhibitor Dap. The determination that miRNAs were required for stem cell division suggests that miRNAs might be part of a mechanism that makes stem cells insensitive to environmental signals that normally stop the cell cycle. Because miRNAs are a novel class of genes involved in human tumorigenesis, the group suggests that it is tempting to speculate that miRNAs could have a similar role in cancer cells.
Title: Stem cell division is regulated by the microRNA pathway.
Authors: Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H
Journal: Nature, Vol 435, Issue 7044: 974-8
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Laura Poliseno et al (2006) examined the involvement of microRNAs in modulation of the angiogenic properties of human umbilical vein endothelial cells (HUVECs). The researchers performed large-scale analysis of miRNA expression in HUVECs and found that 15 highly expressed miRNAs have the receptors of angiogenic factors as putative targets. In particular, the group demonstrated that the miR-221/miR-222 family modulates the angiogenic activity of stem cell factor (SCF) by targeting its receptor, c-Kit. Based on results, the researchers suggest that the interaction between miR-221/miR-222 and c-kit might also have a role in the formation of new vessels that occur in physiological and pathologic conditions (tumor growth). Further validation of the information gleaned in this study is expected to help discover the miRNA network responsible for the fine-tuning of the angiogenic process and, in the long term, to find new therapeutic approaches to modulate angiogenesis.
Title: MicroRNAs modulate the angiogenic properties of HUVECs.
Authors: Poliseno L, Tuccoli A, Mariani L, Evangelista M, Citti L, Woods K, Mercatanti A, Hammond S, Rainaldi G
Journal: Blood, Vol 108, Issue 9: 3068-71
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Title: Radiation-induced response of micro RNA expression in murine embryonic stem cells.
Authors: Ishii H, Saito T
Journal: Med Chem, Vol 2, Issue 6: 555-63
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Title: Methods for analyzing microRNA expression and function during hematopoietic lineage differentiation.
Authors: Min H, Chen CZ
Journal: Methods Mol Biol. 2006;342:209-27.
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Title: MicroRNAs and cell differentiation in mammalian development.
Authors: Song L, Tuan RS
Journal: Birth Defects Res C Embryo Today, Vol 78, Issue 2: 140-9
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Title: MicroRNA: a new player in stem cells.
Authors: Zhang B, Pan X, Anderson TA
Journal: J Cell Physiol, Vol 209, Issue 2: 266-9
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