TY - JOUR
T1 - Mouse Retinal Cell Atlas
T2 - Molecular Identification of over Sixty Amacrine Cell Types
AU - Yan, Wenjun
AU - Laboulaye, Mallory A.
AU - Tran, Nicholas M.
AU - Whitney, Irene E.
AU - Benhar, Inbal
AU - Sanes, Joshua R.
N1 - Publisher Copyright:
Copyright © 2020 the authors
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
KW - GABA
KW - Glycine
KW - Meis2
KW - Neuropeptide
KW - RNA-seq
KW - TCF4
UR - http://www.scopus.com/inward/record.url?scp=85087528284&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0471-20.2020
DO - 10.1523/JNEUROSCI.0471-20.2020
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C2 - 32457074
AN - SCOPUS:85087528284
SN - 0270-6474
VL - 40
SP - 5177
EP - 5195
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 27
ER -