Mouse Retinal Cell Atlas: Molecular Identification of over Sixty Amacrine Cell Types

Wenjun Yan, Mallory A. Laboulaye, Nicholas M. Tran, Irene E. Whitney, Inbal Benhar, Joshua R. Sanes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

168 Scopus citations

Abstract

Amacrine cells (ACs) are a diverse class of interneurons that modulate input from photoreceptors to retinal ganglion cells (RGCs), rendering each RGC type selectively sensitive to particular visual features, which are then relayed to the brain. While many AC types have been identified morphologically and physiologically, they have not been comprehensively classified or molecularly characterized. We used high-throughput single-cell RNA sequencing to profile .32,000 ACs from mice of both sexes and applied computational methods to identify 63 AC types. We identified molecular markers for each type and used them to characterize the morphology of multiple types. We show that they include nearly all previously known AC types as well as many that had not been described. Consistent with previous studies, most of the AC types expressed markers for the canonical inhibitory neurotransmitters GABA or glycine, but several expressed neither or both. In addition, many expressed one or more neuropeptides, and two expressed glutamatergic markers. We also explored transcriptomic relationships among AC types and identified transcription factors expressed by individual or multiple closely related types. Noteworthy among these were Meis2 and Tcf4, expressed by most GABAergic and most glycinergic types, respectively. Together, these results provide a foundation for developmental and functional studies of ACs, as well as means for genetically accessing them. Along with previous molecular, physiological, and morphologic analyses, they establish the existence of at least 130 neuronal types and nearly 140 cell types in the mouse retina.

Original languageEnglish
Pages (from-to)5177-5195
Number of pages19
JournalJournal of Neuroscience
Volume40
Issue number27
DOIs
StatePublished - 1 Jul 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2020 the authors

Keywords

  • GABA
  • Glycine
  • Meis2
  • Neuropeptide
  • RNA-seq
  • TCF4

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