DeCoN: Genome-wide Analysis of In Vivo Transcriptional Dynamics during Pyramidal Neuron Fate Selection in Neocortex

被引:181
作者
Molyneaux, Bradley J. [1 ]
Goff, Loyal A. [1 ,2 ,3 ]
Brettler, Andrea C. [1 ]
Chen, Hsu-Hsin [1 ]
Brown, Juliana R. [1 ]
Hrvatin, Sinisa [1 ]
Rinn, John L. [1 ,2 ,4 ]
Arlotta, Paola [1 ,2 ]
机构
[1] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
[2] Broad Inst MIT & Harvard, Cambridge, MA 02139 USA
[3] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA
[4] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA
关键词
LONG NONCODING RNAS; TRANSLATIONAL PROFILING APPROACH; SUBTYPE-SPECIFIC GENES; CNS CELL-TYPES; CEREBRAL-CORTEX; HUMAN BRAIN; SUBPLATE NEURONS; MOUSE; EXPRESSION; DIFFERENTIATION;
D O I
10.1016/j.neuron.2014.12.024
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:275 / 288
页数:14
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