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

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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.

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Journal

Journal ID (iso-abbrev): Neuron

Title: Neuron

ISSN (Electronic): 1097-4199

ISSN (Print): 0896-6273

Publication date (Electronic): Jan 21 2015

Volume: 85

Issue: 2

Affiliations

[1 ] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.

[2 ] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

[3 ] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. Electronic address: john_rinn@harvard.edu.

[4 ] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA. Electronic address: paola_arlotta@harvard.edu.

Article

Publisher Item ID: S0896-6273(14)01133-7 Mid ID: NIHMS650392

DOI: 10.1016/j.neuron.2014.12.024

PubMed ID: 25556833

SO-VID: 9cafb8ae-1ae4-43fe-a7aa-b7e29d2a541a

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