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Genome Biol. 2016 Apr 14;17:67. doi: 10.1186/s13059-016-0932-1.

Single-cell analysis of long non-coding RNAs in the developing human neocortex.

Liu SJ1,2,3, Nowakowski TJ2,4,3, Pollen AA2,4,3, Lui JH2,4,3,5, Horlbeck MA6,7,8,9,3, Attenello FJ1,2,3, He D1,2,3, Weissman JS6,7,8,9,3, Kriegstein AR2,4,3, Diaz AA10,11,12, Lim DA13,14,15,16.

Author information

1
Department of Neurological Surgery, University of California, San Francisco, Ray and Dagmar Dolby Regeneration Medicine Building, 35 Medical Center Way, RMB 1037, San Francisco, CA, 94143, USA.
2
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA.
3
University of California, San Francisco, San Francisco, CA, 94143, USA.
4
Department of Neurology, San Francisco, CA, 94143, USA.
5
Present Address: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA.
6
Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94143, USA.
7
Howard Hughes Medical Institute, San Francisco, CA, 94143, USA.
8
California Institute for Quantitative Biomedical Research, San Francisco, CA, 94143, USA.
9
Center for RNA Systems Biology, San Francisco, CA, 94143, USA.
10
Department of Neurological Surgery, University of California, San Francisco, Ray and Dagmar Dolby Regeneration Medicine Building, 35 Medical Center Way, RMB 1037, San Francisco, CA, 94143, USA. Aaron.Diaz@ucsf.edu.
11
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA. Aaron.Diaz@ucsf.edu.
12
University of California, San Francisco, San Francisco, CA, 94143, USA. Aaron.Diaz@ucsf.edu.
13
Department of Neurological Surgery, University of California, San Francisco, Ray and Dagmar Dolby Regeneration Medicine Building, 35 Medical Center Way, RMB 1037, San Francisco, CA, 94143, USA. Daniel.Lim@ucsf.edu.
14
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA. Daniel.Lim@ucsf.edu.
15
University of California, San Francisco, San Francisco, CA, 94143, USA. Daniel.Lim@ucsf.edu.
16
San Francisco Veterans Affairs Medical Center, San Francisco, CA, 94121, USA. Daniel.Lim@ucsf.edu.

Abstract

BACKGROUND:

Long non-coding RNAs (lncRNAs) comprise a diverse class of transcripts that can regulate molecular and cellular processes in brain development and disease. LncRNAs exhibit cell type- and tissue-specific expression, but little is known about the expression and function of lncRNAs in the developing human brain. Furthermore, it has been unclear whether lncRNAs are highly expressed in subsets of cells within tissues, despite appearing lowly expressed in bulk populations.

RESULTS:

We use strand-specific RNA-seq to deeply profile lncRNAs from polyadenylated and total RNA obtained from human neocortex at different stages of development, and we apply this reference to analyze the transcriptomes of single cells. While lncRNAs are generally detected at low levels in bulk tissues, single-cell transcriptomics of hundreds of neocortex cells reveal that many lncRNAs are abundantly expressed in individual cells and are cell type-specific. Notably, LOC646329 is a lncRNA enriched in single radial glia cells but is detected at low abundance in tissues. CRISPRi knockdown of LOC646329 indicates that this lncRNA regulates cell proliferation.

CONCLUSION:

The discrete and abundant expression of lncRNAs among individual cells has important implications for both their biological function and utility for distinguishing neural cell types.

KEYWORDS:

CRISPRi; Developing brain; Single-cell RNA-seq; lncRNA

PMID:
27081004
PMCID:
PMC4831157
DOI:
10.1186/s13059-016-0932-1
[Indexed for MEDLINE]
Free PMC Article

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