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

Abstract

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 pathway/genes 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 genes/pathways 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 pathway(s) in rescue types of experiments based on the use of Nf1-deficient BMSCs and osteoblast differentiation assays as primary readout.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2020
Accession Number
AD1105469

Entities

People

  • Florent Elefteriou

Organizations

  • Baylor College of Medicine

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Biomedical Research
  • Bone Fractures
  • Bone Marrow
  • Bones
  • Cells
  • Culture Techniques
  • Department Of Defense
  • Electronic Mail
  • Gene Expression
  • Genes
  • Genetic Phenomena
  • Genetic Structures
  • Genetics
  • Genotypes
  • Medical Personnel
  • Mutations
  • Osteoblasts

Fields of Study

  • Biology

Readers

  • Immunology and Pathology
  • Molecular and genetic basis of cancer.
  • Trauma Surgery or Emergency Medicine.