Identifier Results

Field Value
Identifier nemo:dat-717krsa
Dataset Name A single-cell long-read investigation of mammalian isoform expression reveals regulation along brain regions, cell types, and development
Version NA
Release Date NA
Source Data URL
Dataset Collection URL NA
Description RNA isoforms influence cell identity and function. Until recently, technological limitations prevented a genome-wide appraisal of isoform influence on cell identity in various parts of the brain. Using enhanced long-read single-cell isoform sequencing, we comprehensively analyze RNA isoforms in multiple mouse brain regions, cell subtypes, and developmental timepoints from postnatal day 14 (P14) to adult (P56). For 72% of genes, full-length isoform expression varies along one or more axes of phenotypic origin, underscoring the pervasiveness of isoform regulation across multiple scales. As expected, splicing varies strongly between cell types. However, certain gene classes including neurotransmitter release and reuptake as well as synapse turnover, harbor significant variability in the same cell type across anatomical regions, suggesting differences in network activity may influence cell-type identity. Neurons and glia show distinct regulation at transcription start sites and polyadenylation sites. Developmental patterns of cell-type specific splicing are especially pronounced in the murine adolescent transition from P21 to P28. The same cell type traced across development shows more isoform variability than across adult anatomical regions, indicating a coordinated modulation of functional programs dictating neural development. As most cell-type specific exons in P56 mouse hippocampus behave similarly in newly generated data from human hippocampi, these principles may be extrapolated to human brain. However, human brains have evolved additional cell-type specificity in splicing, suggesting gain-of-function isoforms. Taken together, we present a detailed single-cell atlas of full-length brain isoform regulation across development and anatomical regions, providing a previously unappreciated degree of isoform variability across multiple scales of the brain.
Keywords long-read, single-cell, isoform, alternative splicing, development, brain region
Total Files in Collection 0
Total Size in Collection (in GB) 0.0
Authors Anoushka Joglekar, Wen Hu, Bei Zhang, Oleksandr Narykov, Mark Diekhans, Jordan Marrocco, Jennifer Balacco, Lishomwa C Ndhlovu, Teresa A Milner, Olivier Fedrigo, Erich D Jarvis, Gloria Sheynkman, Dmitry Korkin, M. Elizabeth Ross, Hagen U. Tilgner
Organization Weill Cornell Medicine, New York, NY
Contact Person Anoushka Joglekar
Contact E-Mail
External Identifier
Grant Name 1RF1MH121267-01, 1R01GM135247-01
Consortium BICCN
Data Repository NeMO
Data Repository RRID RRID:SCR_016152
Data License Public data available under CC BY 4.0; controlled access data subject to data use certification
Data Access
Community Standards
Study Organism Mus musculus, Homo sapiens
Protocol ID

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