FMR1 Deficiency Alters Self-Renewal and Proliferation of Mouse Embryonic Cells
作者： Shyam Sundhar Bale , Nima Saeidi , Srivatsan Kidambi , Martin L. Yarmush , Monica Casali
DOI: 10.1142/S1793984415500038
关键词: SOX2 、 Oct-4 、 Stem cell 、 Homeobox protein NANOG 、 Molecular biology 、 Biology 、 Gene silencing 、 RNA interference 、 FMR1 、 Small hairpin RNA
摘要: The regulation of embryonic stem (ES) cell self-renewal and pluripotency is based upon highly orchestrated transcription factor networks. RNA inhibition has been demonstrated to affect ES function by altering gene expression levels that are critical the maintenance differentiation cells. Fragile X mental retardation protein (FMRP) a selective RNA-binding can act as translational repressor for bound mRNA regulates variety transcripts in numerous adult absence FMRP results most common form inherited intellectual disability, syndrome. In an effort determine role during development, we silenced (FMR1) using short hairpin (shRNA). Prior induction, analyzed phenotype FMR1 knock down (FMR1-kd) mouse cells their undifferentiated state. Herein, report FMR1-kd proliferate at greater rate than wild-type resulting 25% reduction doubling time. were found have increased three genes (OCT-4, Sox2, Nanog) Moreover, failed downregulate OCT-4 programs abnormal fate decisions vitro. These demonstrate unexpected correlation between suggesting involved silencing commencement programs.
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