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Title: Human Embryonic Stem Cell-derived Neural Stem Cells: Derivation, Differentiation and MicroRNA Regulation
Keywords: Human embryonic stem cell, neural stem cell, microRNA, glial progenitor, self-renewal, differentiation
Issue Date: 25-Jan-2013
Source: KWANG WEI XIN TIMOTHY (2013-01-25). Human Embryonic Stem Cell-derived Neural Stem Cells: Derivation, Differentiation and MicroRNA Regulation. ScholarBank@NUS Repository.
Abstract: There is burgeoning interest in neural stem/progenitor cells (NSCs) for both developmental research and cell-based therapeutics. Although the functional properties of human NSCs, in terms of their tumor-homing, in vivo regenerative and in vitro differentiation capacities, have been extensively studied, the molecular mechanisms underlying their self-renewal and differentiation are poorly understood. Here, NSCs were derived from human embryonic stem cells (hESCs) and further differentiated into NG2+ glial progenitor cells (GPCs). PAX6 and SOX2, two transcription factors that characterize NSCs and function as key determinants of the human neural fate, were observed to be downregulated in hESC-derived NSCs upon GPC differentiation. microRNAs (miRNAs) have been implicated in NSC self-renewal and fate commitment, and thus are plausibly involved in the downregulation of PAX6 and SOX2 in NSCs during GPC differentiation. Utilizing miRNA microarrays, four miRNAs, miR-21, -22, -145 and -221, were identified to be upregulated in GPCs compared with NSCs, among which miR-22 and miR-221 were demonstrated to be putative PAX6-targeting miRNAs. The ectopic expression of miR-145 repressed SOX2 protein expression in human NSCs, while its inhibition induced the opposite, thus suggesting that miR-145 regulates SOX2 expression in NSCs and possibly modulates the transition from multipotency to neural fate commitment. Together, this study highlights a mechanistic role of miRNAs in regulating self-renewal and lineage specification in human NSCs by possibly acting on key fate determining transcription factors.
Appears in Collections:Ph.D Theses (Open)

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