A Translational Profiling Approach for the Molecular Characterization of CNS Cell Types

Myriam Heiman, Anne Schaefer, Shiaoching Gong, Jayms D. Peterson, Michelle Day, Keri E. Ramsey, Mayte Suárez-Fariñas, Cordelia Schwarz, Dietrich A. Stephan, D. James Surmeier, Paul Greengard, Nathaniel Heintz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

731 Scopus citations

Abstract

The cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations. Using bacterial artificial chromosome (BAC) transgenic mice that express EGFP-tagged ribosomal protein L10a in defined cell populations, we have developed a methodology for affinity purification of polysomal mRNAs from genetically defined cell populations in the brain. The utility of this approach is illustrated by the comparative analysis of four types of neurons, revealing hundreds of genes that distinguish these four cell populations. We find that even two morphologically indistinguishable, intermixed subclasses of medium spiny neurons display vastly different translational profiles and present examples of the physiological significance of such differences. This genetically targeted translating ribosome affinity purification (TRAP) methodology is a generalizable method useful for the identification of molecular changes in any genetically defined cell type in response to genetic alterations, disease, or pharmacological perturbations.

Original languageEnglish (US)
Pages (from-to)738-748
Number of pages11
JournalCell
Volume135
Issue number4
DOIs
StatePublished - Nov 14 2008

Keywords

  • CELLBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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