Single-cell long-read sequencing-based mapping reveals specialized splicing patterns in developing and adult mouse and human brain.

Autor: Joglekar A; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.; Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.; New York Genome Center, New York, NY, USA., Hu W; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.; Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA., Zhang B; Spatial Genomics, Inc., Pasadena, CA, USA., Narykov O; Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA, USA.; Computer Science Department, Worcester Polytechnic Institute, Worcester, MA, USA.; Data Science Program, Worcester Polytechnic Institute, Worcester, MA, USA., Diekhans M; UC Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA, USA., Marrocco J; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.; Department of Biology, Touro University, New York, NY, USA.; Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA., Balacco J; Vertebrate Genome Lab, The Rockefeller University, New York, NY, USA., Ndhlovu LC; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.; Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA., Milner TA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA., Fedrigo O; Vertebrate Genome Lab, The Rockefeller University, New York, NY, USA., Jarvis ED; Vertebrate Genome Lab, The Rockefeller University, New York, NY, USA.; Laboratory of Neurogenetics of Language, The Rockefeller University, New York, NY, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Sheynkman G; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USA.; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.; UVA Comprehensive Cancer Center, University of Virginia, Charlottesville, VA, USA., Korkin D; Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA, USA.; Computer Science Department, Worcester Polytechnic Institute, Worcester, MA, USA.; Data Science Program, Worcester Polytechnic Institute, Worcester, MA, USA., Ross ME; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.; Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA., Tilgner HU; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. hut2006@med.cornell.edu.; Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA. hut2006@med.cornell.edu.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2024 Jun; Vol. 27 (6), pp. 1051-1063. Date of Electronic Publication: 2024 Apr 09.
DOI: 10.1038/s41593-024-01616-4
Abstrakt: RNA isoforms influence cell identity and function. However, a comprehensive brain isoform map was lacking. We analyze single-cell RNA isoforms across brain regions, cell subtypes, developmental time points and species. For 72% of genes, full-length isoform expression varies along one or more axes. Splicing, transcription start and polyadenylation sites vary strongly between cell types, influence protein architecture and associate with disease-linked variation. Additionally, neurotransmitter transport and synapse turnover genes harbor cell-type variability across anatomical regions. Regulation of cell-type-specific splicing is pronounced in the postnatal day 21-to-postnatal day 28 adolescent transition. Developmental isoform regulation is stronger than regional regulation for the same cell type. Cell-type-specific isoform regulation in mice is mostly maintained in the human hippocampus, allowing extrapolation to the human brain. Conversely, the human brain harbors additional cell-type specificity, suggesting gain-of-function isoforms. Together, this detailed single-cell atlas of full-length isoform regulation across development, anatomical regions and species reveals an unappreciated degree of isoform variability across multiple axes.
(© 2024. The Author(s).)
Databáze: MEDLINE
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