title: Single-cell analysis of long non-coding RNAs in the developing human neocortex.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA.|University of California, San Francisco, San Francisco, CA, 94143, USA.
authors.forename: Siyuan John
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA.|Department of Neurology, San Francisco, CA, 94143, USA.|University of California, San Francisco, San Francisco, CA, 94143, USA.
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Nowakowski
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA.|Department of Neurology, San Francisco, CA, 94143, USA.|University of California, San Francisco, San Francisco, CA, 94143, USA.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Pollen
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA.|Department of Neurology, San Francisco, CA, 94143, USA.|University of California, San Francisco, San Francisco, CA, 94143, USA.|Present Address: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Lui
authors.affiliation: Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94143, USA.|Howard Hughes Medical Institute, San Francisco, CA, 94143, USA.|California Institute for Quantitative Biomedical Research, San Francisco, CA, 94143, USA.|Center for RNA Systems Biology, San Francisco, CA, 94143, USA.|University of California, San Francisco, San Francisco, CA, 94143, USA.
authors.forename: Max A
authors.initials: MA
authors.lastname: Horlbeck
authors.affiliation: 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.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA.|University of California, San Francisco, San Francisco, CA, 94143, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Attenello
authors.affiliation: 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.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA.|University of California, San Francisco, San Francisco, CA, 94143, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Cellular and Molecular Pharmacology, San Francisco, CA, 94143, USA.|Howard Hughes Medical Institute, San Francisco, CA, 94143, USA.|California Institute for Quantitative Biomedical Research, San Francisco, CA, 94143, USA.|Center for RNA Systems Biology, San Francisco, CA, 94143, USA.|University of California, San Francisco, San Francisco, CA, 94143, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Weissman
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA.|Department of Neurology, San Francisco, CA, 94143, USA.|University of California, San Francisco, San Francisco, CA, 94143, USA.
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Kriegstein
authors.affiliation: 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.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA. Aaron.Diaz@ucsf.edu.|University of California, San Francisco, San Francisco, CA, 94143, USA. Aaron.Diaz@ucsf.edu.
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Diaz
authors.affiliation: 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.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, 94143, USA. Daniel.Lim@ucsf.edu.|University of California, San Francisco, San Francisco, CA, 94143, USA. Daniel.Lim@ucsf.edu.|San Francisco Veterans Affairs Medical Center, San Francisco, CA, 94121, USA. Daniel.Lim@ucsf.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lim
mesh_terms: D049109:Cell Proliferation; D063928:Ependymoglial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D019579:Neocortex / Q000196:embryology* / Q000378:metabolism; D009928:Organ Specificity; D011247:Pregnancy; D062085:RNA, Long Noncoding / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods; D059010:Single-Cell Analysis / Q000379:methods*
chemical_list: D062085:RNA, Long Noncoding
keywords: CRISPRi; Developing brain; Single-cell RNA-seq; lncRNA