DeCoN: genome-wide analysis of in vivo transcriptional dynamics during pyramidal neuron fate selection in neocortex

Neuron. 2015 Jan 21;85(2):275-288. doi: 10.1016/j.neuron.2014.12.024. Epub 2014 Dec 31.

Abstract

Neuronal development requires a complex choreography of transcriptional decisions to obtain specific cellular identities. Realizing the ultimate goal of identifying genome-wide signatures that define and drive specific neuronal fates has been hampered by enormous complexity in both time and space during development. Here, we have paired high-throughput purification of pyramidal neuron subclasses with deep profiling of spatiotemporal transcriptional dynamics during corticogenesis to resolve lineage choice decisions. We identified numerous features ranging from spatial and temporal usage of alternative mRNA isoforms and promoters to a host of mRNA genes modulated during fate specification. Notably, we uncovered numerous long noncoding RNAs with restricted temporal and cell-type-specific expression. To facilitate future exploration, we provide an interactive online database to enable multidimensional data mining and dissemination. This multifaceted study generates a powerful resource and informs understanding of the transcriptional regulation underlying pyramidal neuron diversity in the neocortex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation / genetics*
  • Corpus Callosum / cytology
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / genetics*
  • Matrix Attachment Region Binding Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Motor Neurons
  • Neocortex / metabolism*
  • Neurogenesis / genetics
  • Neurons / metabolism
  • Pyramidal Cells / metabolism*
  • Pyramidal Tracts / cytology
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics*
  • Repressor Proteins / metabolism
  • Transcription Factors / metabolism
  • Transcriptome*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Bcl11b protein, mouse
  • Matrix Attachment Region Binding Proteins
  • RNA, Long Noncoding
  • RNA, Messenger
  • Repressor Proteins
  • SATB2 protein, mouse
  • Tle4 protein, mouse
  • Transcription Factors
  • Tumor Suppressor Proteins

Associated data

  • GEO/GSE63482