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An Unbiased Approach to Search for the Cause of the Reduced Osteogenic Differentiation Potential of NF1-Deficient Osteoprogenitors

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Baylor College of Medicine Houston United States

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We will use the critical observation that Nf1- and Nf1-deficient osteoprogenitors are both characterized by constitutive activation of ERK signaling, but only the latter fail to differentiate, to identify ERK-independent pathwaygenes causing the reduced differentiation potential of Nf1-deficient BMSCs, using a nonbiased RNA-Seq approach. The candidate gene signature will be enriched in high confidence genespathways by selecting differentially expressed genes between genotypes conserved between mouse and human BMSCs. The second part of the proposed work will consist in testing, functionally and in vitro, the contribution of selected candidate genes and pathways in rescue types of experiments based on the use of Nf1-deficient BMSCs and osteoblast differentiation assays as primary readout.

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Technical Report,01 Aug 2019,31 Jul 2020



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Approved For Public Release;

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