title: DeCoN: genome-wide analysis of in vivo transcriptional dynamics during pyramidal neuron fate selection in neocortex.
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.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, United States.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Molyneaux
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, United States.|Broad Institute of MIT and Harvard, Cambridge, MA, 02139, United States.|Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, 02139, United States.
authors.forename: Loyal A
authors.initials: LA
authors.lastname: Goff
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, United States.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Brettler
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, United States.
authors.forename: Hsu-Hsin
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, United States.
authors.forename: Siniša
authors.initials: S
authors.lastname: Hrvatin
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, United States.|Broad Institute of MIT and Harvard, Cambridge, MA, 02139, United States.|Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, United States.
authors.forename: John L
authors.initials: JL
authors.lastname: Rinn
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, United States.|Broad Institute of MIT and Harvard, Cambridge, MA, 02139, United States.
authors.forename: Paola
authors.initials: P
authors.lastname: Arlotta
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D003337:Corpus Callosum / Q000166:cytology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009046:Motor Neurons; D019579:Neocortex / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000166:cytology; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: C511143:Bcl11b protein, mouse; D036961:Matrix Attachment Region Binding Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012097:Repressor Proteins; C501473:SATB2 protein, mouse; C434949:Tle4 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins