Single-cell transcriptional analysis of neuronal progenitors

Neuron. 2003 Apr 24;38(2):161-75. doi: 10.1016/s0896-6273(03)00229-0.

Abstract

The extraordinary cellular heterogeneity of the mammalian nervous system has largely hindered the molecular analysis of neuronal identity and diversity. In order to uncover mechanisms involved in neuronal differentiation and diversification, we have monitored the expression profiles of individual neurons and progenitor cells collected from dissociated tissue or captured from intact slices. We demonstrate that this technique provides a sensitive and reproducible representation of the single-cell transcriptome. In the olfactory system, hundreds of transcriptional differences were identified between olfactory progenitors and mature sensory neurons, enabling us to define the large variety of signaling pathways expressed by individual progenitors at a precise developmental stage. Finally, we show that regional differences in gene expression can be predicted from transcriptional analysis of single neuronal precursors isolated by laser capture from defined areas of the developing brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation
  • Cell Separation / instrumentation
  • Cell Separation / methods
  • Cells, Cultured
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / biosynthesis
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Developmental
  • Humans
  • Lasers
  • Mice
  • Neuroglia / chemistry
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Neurons / chemistry
  • Neurons / cytology
  • Neurons / metabolism*
  • Neurons, Afferent / chemistry
  • Neurons, Afferent / cytology
  • Neurons, Afferent / metabolism
  • Nucleic Acid Hybridization
  • Olfactory Mucosa / cytology
  • Olfactory Mucosa / embryology
  • Olfactory Mucosa / innervation
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Signal Transduction / physiology
  • Stem Cells / chemistry
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / biosynthesis
  • Transcription, Genetic / physiology*

Substances

  • ASCL1 protein, human
  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA, Complementary
  • DNA-Binding Proteins
  • RNA, Messenger
  • Transcription Factors