期刊
CELL
卷 135, 期 4, 页码 738-748出版社
CELL PRESS
DOI: 10.1016/j.cell.2008.10.028
关键词
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资金
- Howard Hughes Medical Institute Funding Source: Medline
- NCRR NIH HHS [5UL1RR024143] Funding Source: Medline
- NIA NIH HHS [P01 AG009464-16A1, P01 AG009464-17, P01 AG009464, AG09464] Funding Source: Medline
- NIDA NIH HHS [P01 DA010044-09, F32 DA021487-02, 5F32DA021487, P01 DA010044-10, DA10044, F32 DA021487, F32 DA021487-01, P01 DA010044-11, P01 DA010044] Funding Source: Medline
- NIMH NIH HHS [P50 MH074866-040005, P50 MH074866-030005, P50 MH074866-020005, P50 MH074866-010005, P50 MH074866-02, P50 MH074866-017204, P50 MH074866-019001, P50 MH074866-030002, P50 MH074866-019002, P50 MH074866-020002, P50 MH074866-049001, P50 MH074866-039002, P50 MH074866-010001, P50 MH074866-029002, P50 MH074866-030001, P50 MH074866-020001, P50 MH074866, P50 MH074866-029001, P50 MH074866-03, P50 MH074866-040002, P50 MH074866-04, P50 MH074866-01, P50 MH074866-010002, P50 MH074866-049002, P50 MH074866-040001, MH074866, P50 MH074866-039001] Funding Source: Medline
- NINDS NIH HHS [R37 NS034696-12, R37 NS034696, R01 NS034696, R37 NS034696-11, R37 NS034696-13, NS34696] Funding Source: Medline
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.
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