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Nat Neurosci. 2015 May;18(5):637-46. doi: 10.1038/nn.3980. Epub 2015 Mar 3.

Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex.

Author information

1
1] Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA. [2] Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA. [3] Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts, USA.
2
1] Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. [2] Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
3
1] Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA. [2] Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA. [3] Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts, USA. [4] Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA. [5] Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA. [6] Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

Abstract

The human cerebral cortex depends for its normal development and size on a precisely controlled balance between self-renewal and differentiation of diverse neural progenitor cells. Specialized progenitors that are common in humans but virtually absent in rodents, called outer radial glia (ORG), have been suggested to be crucial to the evolutionary expansion of the human cortex. We combined progenitor subtype-specific sorting with transcriptome-wide RNA sequencing to identify genes enriched in human ORG, which included targets of the transcription factor neurogenin and previously uncharacterized, evolutionarily dynamic long noncoding RNAs. Activating the neurogenin pathway in ferret progenitors promoted delamination and outward migration. Finally, single-cell transcriptional profiling in human, ferret and mouse revealed more cells coexpressing proneural neurogenin targets in human than in other species, suggesting greater neuronal lineage commitment and differentiation of self-renewing progenitors. Thus, we find that the abundance of human ORG is paralleled by increased transcriptional heterogeneity of cortical progenitors.

PMID:
25734491
PMCID:
PMC5568903
DOI:
10.1038/nn.3980
[Indexed for MEDLINE]
Free PMC Article

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