LKB1 and AMPK instruct cone nuclear position to modify visual function

Burger, Courtney A.; Albrecht, Nicholas E.; Jiang, Danye; Liang, Justine H; Poché, Ross A.; Samuel, Melanie A.

doi:10.1016/j.celrep.2021.108698

Cited by 7 publications

(7 citation statements)

References 74 publications

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“…For example, the two AC subgroups, GABAergic and glycinergic ACs, show distinct sublayer localization within the inner nuclear layer (INL) with GABAergic ACs basally positioned closer to the ganglion cell layer (GCL) in general 8 . Furthermore, previous studies have suggested that the laminar position of cell somas could affect its function and neurites remodeling of interacting cells [9][10][11] .…”

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confidence: 99%

Spatial organization of the mouse retina at single cell resolution by MERFISH

Choi

Ferdous

et al. 2023

Nat Commun

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The visual signal processing in the retina requires the precise organization of diverse neuronal types working in concert. While single-cell omics studies have identified more than 120 different neuronal subtypes in the mouse retina, little is known about their spatial organization. Here, we generated the single-cell spatial atlas of the mouse retina using multiplexed error-robust fluorescence in situ hybridization (MERFISH). We profiled over 390,000 cells and identified all major cell types and nearly all subtypes through the integration with reference single-cell RNA sequencing (scRNA-seq) data. Our spatial atlas allowed simultaneous examination of nearly all cell subtypes in the retina, revealing 8 previously unknown displaced amacrine cell subtypes and establishing the connection between the molecular classification of many cell subtypes and their spatial arrangement. Furthermore, we identified spatially dependent differential gene expression between subtypes, suggesting the possibility of functional tuning of neuronal types based on location.

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confidence: 99%

Spatial organization of the mouse retina at single cell resolution by MERFISH

Choi

Ferdous

et al. 2023

Nat Commun

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“…For example, the two amacrine cell (AC) subgroups, GABAergic and glycinergic ACs, show distinct sublayer localization within the inner nuclear layer (INL) with GABAergic ACs basally positioned closer to the ganglion cell layer (GCL) in general (Voinescu et al, 2009). Furthermore, it has been reported that the laminar position of the cell nuclei could affect its function and neurites remodeling of interacting cells (Burger et al, 2021; Nemitz et al, 2021; Sonntag et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Spatial organization of the mouse retina at single cell resolution

Choi

Ferdous

et al. 2022

Preprint

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The visual signal processing in the retina requires the precise organization of diverse neuronal types working in concert. We performed spatial transcriptomic profiling of over 100,000 cells from the mouse retia, uncovering the spatial distribution of all major retina cell types with over 100 cell subtypes. Our data revealed that the retina is organized in a laminar structure at the major cell type and subgroup level, both of which has strong correlation with the birth order of the cell. In contrast, overall random dispersion of cells within sub-laminar layers indicates that retinal mosaics are driven by dendritic field patterning rather than neuron soma placement. Through the integration of single cell transcriptomic and spatial data, we have generated the first comprehensive spatial single cell reference atlas of the mouse retina, a resource to the community and an essential step toward gaining a comprehensive understanding of the mechanism of retinal function.

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“…While postmitotic movements of cone nuclei have been reported in mice, the signals and molecular pathways controlling this process have not been resolved [38,39]. A study of ectopically located cones in GRF2-KO mice suggested a potential role for GRF2 and CDC42 in the formation/structure of PARcontaining, polarity-related macromolecular complexes [40,41], and the serine/threonine kinase LKB1 as well as one of its substrates, AMPK, have also been identified as regulators of cone nuclear positioning [42]. Our observations suggest that in human retinae apical cones extend processes basally, prior to relocation, in an active process rather than one based on simple somal displacement by newly generated rods.…”

Section: Discussionmentioning

confidence: 99%

Generation of a Cone Photoreceptor-specific GNGT2 Reporter Line in Human Pluripotent Stem Cells

et al. 2022

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Fluorescent reporter lines generated in human pluripotent stem cells are a highly useful tool to track, isolate and analyse cell types and lineages in live cultures. Here, we generate the first human cone photoreceptor reporter cell line by CRISPR/Cas9 genome editing of a human embryonic stem cell (hESC) line to tag both alleles of the Guanine nucleotide-binding protein subunit gamma-T2 (GNGT2) gene with a mCherry reporter cassette. Three-dimensional optic vesicle-like structures were produced to verify reporter fidelity and track cones throughout their development in culture. The GNGT2-T2A-mCherry hESC line faithfully and robustly labels GNGT2-expressing cones throughout the entirety of their differentiation in vitro, recapitulating normal fetal expression of this gene. Our observations indicate that human cones undergo significant migratory activity during the course of differentiation in vitro. Consistent with this, our analysis of human fetal retinae from different stages of development finds positional differences of the cone population depending on their state of maturation. This novel reporter line will provide a useful tool for investigating human cone development and disease.

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LKB1 and AMPK instruct cone nuclear position to modify visual function

Cited by 7 publications

References 74 publications

Spatial organization of the mouse retina at single cell resolution by MERFISH

Spatial organization of the mouse retina at single cell resolution by MERFISH

Spatial organization of the mouse retina at single cell resolution

Generation of a Cone Photoreceptor-specific GNGT2 Reporter Line in Human Pluripotent Stem Cells

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