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Molecular characterization of projection neuron subtypes in the mouse olfactory bulb.

Sara Zeppilli | Tobias Ackels | Robin Attey | Nell Klimpert | Kimberly D Ritola | Stefan Boeing | Anton Crombach | Andreas T Schaefer | Alexander Fleischmann
eLife | 2021

Projection neurons (PNs) in the mammalian olfactory bulb (OB) receive input from the nose and project to diverse cortical and subcortical areas. Morphological and physiological studies have highlighted functional heterogeneity, yet no molecular markers have been described that delineate PN subtypes. Here, we used viral injections into olfactory cortex and fluorescent nucleus sorting to enrich PNs for high-throughput single nucleus and bulk RNA deep sequencing. Transcriptome analysis and RNA in situ hybridization identified distinct mitral and tufted cell populations with characteristic transcription factor network topology, cell adhesion, and excitability-related gene expression. Finally, we describe a new computational approach for integrating bulk and snRNA-seq data and provide evidence that different mitral cell populations preferentially project to different target regions. Together, we have identified potential molecular and gene regulatory mechanisms underlying PN diversity and provide new molecular entry points into studying the diverse functional roles of mitral and tufted cell subtypes.

Pubmed ID: 34292150

Associated grants

  • Agency: Howard Hughes Medical Institute, United States
  • Agency: Wellcome Trust, United Kingdom
    Id: FC001153
  • Agency: Cancer Research UK, United Kingdom
    Id: FC001153
  • Agency: NIH HHS, United States
    Id: S10 OD025181
  • Agency: Medical Research Council, United Kingdom
    Id: FC001153
  • Agency: NIDCD NIH HHS, United States
    Id: R01 DC017437
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Wellcome Trust, United Kingdom
    Id: 110174/Z/15/Z
  • Agency: NINDS NIH HHS, United States
    Id: U19 NS112953
  • Agency: NINDS NIH HHS, United States
    Id: P30 NS072030
  • Agency: Arthritis Research UK, United Kingdom
    Id: FC001153
  • Agency: NCRR NIH HHS, United States
    Id: S10 RR021051

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