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Curr Biol. 2018 Sep 24;28(18):2910-2920.e2. doi: 10.1016/j.cub.2018.07.062. Epub 2018 Sep 13.

A Single-Cell Transcriptional Atlas of the Developing Murine Cerebellum.

Author information

1
Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
2
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
3
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
4
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: john.easton@stjude.org.
5
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: paul.northcott@stjude.org.
6
Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: charles.gawad@stjude.org.

Abstract

The cerebellum develops from a restricted number of cell types that precisely organize to form the circuitry that controls sensory-motor coordination and some higher-order cognitive processes. To acquire an enhanced understanding of the molecular processes that mediate cerebellar development, we performed single-cell RNA-sequencing of 39,245 murine cerebellar cells at twelve critical developmental time points. Using recognized lineage markers, we confirmed that the single-cell data accurately recapitulate cerebellar development. We then followed distinct populations from emergence through migration and differentiation, and determined the associated transcriptional cascades. After identifying key lineage commitment decisions, focused analyses uncovered waves of transcription factor expression at those branching points. Finally, we created Cell Seek, a flexible online interface that facilitates exploration of the dataset. Our study provides a transcriptional summarization of cerebellar development at single-cell resolution that will serve as a valuable resource for future investigations of cerebellar development, neurobiology, and disease.

KEYWORDS:

cerebellum; mouse development; single-cell sequencing

PMID:
30220501
DOI:
10.1016/j.cub.2018.07.062
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