miR-125b Is an adhesion-regulated microRNA that protects mesenchymal stem cells from anoikis.

作者: Xiang Yu , Daniel M. Cohen , Christopher S. Chen

DOI: 10.1002/STEM.1064

关键词: AnoikisEmbryonic stem cellCell cultureInduced pluripotent stem cellCell adhesionBiologyMesenchymal stem cellStem cellReprogrammingCell biology

摘要: Mesenchymal stem cells (MSCs) have the capacity for multilineage differentiation and are being explored as a source cell-based therapies. Previous studies shown that adhesion to extracellular matrix plays critical role in guiding MSC distinct lineages. Here, we conducted focused screen of microRNAs reveal one microRNA, miR-125b, whose expression changes function cell adhesion. miR-125b was upregulated by limiting cell-matrix using micropatterned substrates, knocking down beta5 integrin or placing suspension culture. Interestingly, noted suspending human MSCs (hMSCs) did not induce substantial apoptosis (anoikis) is typically observed adherent cells. Although appeared some effects on hMSC differentiation, demonstrated striking protecting hMSCs from anoikis. Knockdown increased anoikis while expressing mimic protected Mechanistic against increasing ERK phosphorylation suppressing p53. Lastly, found quite limited endothelial mouse embryonic fibroblasts (MEFs). The rapid normally antagonized transfection mimic, suggesting can confer resistance multiple types. We also endogenous significantly during reprogramming MEFs induced pluripotent cells, may be associated with populations. Collectively, these observations demonstrate novel link between adhesion, expression, cell-specific survival program triggered adhesion-limited contexts such might occur early development wound healing. STEM CELLS 2012;30:956–964

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