Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina

Peng, Yi-Rong; Shekhar, Karthik; Yan, Wenjun; Herrmann, Dustin; Sappington, Anna; Bryman, Gregory S.; Zyl, Tavé van; H., Michael Tri; Regev, Aviv; Sanes, Joshua R.

doi:10.1016/j.cell.2019.01.004

Cited by 406 publications

(505 citation statements)

References 85 publications

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“…Moreover, the transcription factor TBX2 has been implicated in subtype specification of Sws1 ‐cones in zebrafish and chicken (Alvarez‐Delfin et al , ; Enright et al , ). In support of these studies, our data showed that TBX2 marks the S‐cones in humans, which is also conserved in macaque (Peng et al , ). Together, these results detailed the molecular profiles and identified marker genes that can distinguish the cone subtypes in humans.…”

Section: Resultssupporting

confidence: 85%

A single‐cell transcriptome atlas of the adult human retina

et al. 2019

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The retina is a specialized neural tissue that senses light and initiates image processing. Although the functional organization of specific retina cells has been well studied, the molecular profile of many cell types remains unclear in humans. To comprehensively profile the human retina, we performed single‐cell RNA sequencing on 20,009 cells from three donors and compiled a reference transcriptome atlas. Using unsupervised clustering analysis, we identified 18 transcriptionally distinct cell populations representing all known neural retinal cells: rod photoreceptors, cone photoreceptors, Müller glia, bipolar cells, amacrine cells, retinal ganglion cells, horizontal cells, astrocytes, and microglia. Our data captured molecular profiles for healthy and putative early degenerating rod photoreceptors, and revealed the loss of MALAT1 expression with longer post‐mortem time, which potentially suggested a novel role of MALAT1 in rod photoreceptor degeneration. We have demonstrated the use of this retina transcriptome atlas to benchmark pluripotent stem cell‐derived cone photoreceptors and an adult Müller glia cell line. This work provides an important reference with unprecedented insights into the transcriptional landscape of human retinal cells, which is fundamental to understanding retinal biology and disease.

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Section: Resultssupporting

confidence: 85%

A single‐cell transcriptome atlas of the adult human retina

et al. 2019

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“…We analyzed scRNA-seq data following the pipeline detailed in Peng et al (2019). Briefly, sample demultiplexing was performed with cellranger mkfastq function (version 2.1.0; 10X Chromium), and reads were aligned to the reference genome mm10 v1.2.0 from cellranger refdata using the cellranger count function with the option --force-cells=6000.…”

Section: Methodsmentioning

confidence: 99%

Molecular identification of sixty-three amacrine cell types completes a mouse retinal cell atlas

Wang

et al. 2020

Preprint

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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 (scRNA-seq) to profile >32,000 ACs from mouse retina, 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 express markers for the canonical inhibitory neurotransmitters GABA or glycine, but several express neither or both. In addition, many express one or more neuropeptides, and two express 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 morphological analyses, they establish the existence of at least 130 neuronal types and nearly 140 cell types in mouse retina. SIGNIFICANCE STATEMENTThe mouse retina is a leading model for analyzing the development, structure, function and pathology of neural circuits. A complete molecular atlas of retinal cell types provides an important foundation for these studies. We used high-throughput single-cell RNA sequencing (scRNA-seq) to characterize the most heterogeneous class of retinal interneurons, amacrine cells, identifying 63 distinct types. The atlas includes types identified previously as well as many novel types. We provide evidence for use of multiple neurotransmitters and neuropeptides and identify transcription factors expressed by groups of closely related types. Combining these results with those obtained previously, we proposed that the mouse retina contains 130 neuronal types, and is therefore comparable in complexity to other regions of the brain.

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“…A shallow sequencing of large cell numbers facilitates comprehensive classification more than a deep sequencing of a small number of cells. Recent scRNA‐seq studies in human and primate adult retina provided a reference transcriptome specific for retinal cell type and offered an advanced discrimination of the mechanisms defining the retinal identity . In primate retina, Peng and colleagues distinguished more than 70 cell types, included extremely rare cell types such as intrinsically photosensitive RGCs, which constitute less than the 0.002% of all the retinal cells .…”

Section: Rare Cell Types and Neuron‐specific Enhancers Can Be Identifmentioning

confidence: 99%

“…Recent scRNA‐seq studies in human and primate adult retina provided a reference transcriptome specific for retinal cell type and offered an advanced discrimination of the mechanisms defining the retinal identity . In primate retina, Peng and colleagues distinguished more than 70 cell types, included extremely rare cell types such as intrinsically photosensitive RGCs, which constitute less than the 0.002% of all the retinal cells . Description of rare cell‐types is particularly thorough when purified cell populations are used as starting material for single‐cell sequencing.…”

Section: Rare Cell Types and Neuron‐specific Enhancers Can Be Identifmentioning

confidence: 99%

Retina Development in Vertebrates: Systems Biology Approaches to Understanding Genetic Programs

Buono

Martı́nez-Morales

2020

BioEssays

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The ontogeny of the vertebrate retina has been a topic of interest to developmental biologists and human geneticists for many decades. Understanding the unfolding of the genetic program that transforms a field of progenitors cells into a functionally complex and multi‐layered sensory organ is a formidable challenge. Although classical genetic studies succeeded in identifying the key regulators of retina specification, understanding the architecture of their gene network and predicting their behavior are still a distant hope. The emergence of next‐generation sequencing platforms revolutionized the field unlocking the access to genome‐wide datasets. Emerging techniques such as RNA‐seq, ChIP‐seq, ATAC‐seq, or single cell RNA‐seq are used to characterize eye developmental programs. These studies provide valuable information on the transcriptional and cis‐regulatory profiles of precursors and differentiated cells, outlining the trajectories that connect each intermediate state. Here, recent systems biology efforts are reviewed to understand the genetic programs shaping the vertebrate retina.

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Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina

Cited by 406 publications

References 85 publications

A single‐cell transcriptome atlas of the adult human retina

A single‐cell transcriptome atlas of the adult human retina

Molecular identification of sixty-three amacrine cell types completes a mouse retinal cell atlas

Retina Development in Vertebrates: Systems Biology Approaches to Understanding Genetic Programs

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