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CyclinD2-mediated regulation of neurogenic output from the retinal ciliary margin is perturbed in albinism

ABSTRACT: CyclinD2-mediated regulation of neurogenic output from the retinal ciliary margin is perturbed in albinism

PROVIDER: PRJNA862370 | ENA |

REPOSITORIES: ENA

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CyclinD2-mediated regulation of neurogenic output from the retinal ciliary margin is perturbed in albinism

Project description:Ciliary margin zone cells have differential neurogenic potential in albino and pigmented eyes. We used single cell RNA sequencing (scRNA-seq) of albino and pigmented eyes to determine transcriptomic changes underlying differential RGC genesis.

2022-11-08 | GSE209764 | GEO

Six3 and Six6 jointly regulate the identities and developmental trajectories of multipotent retinal progenitor cells in the embryonic mouse retina

Project description:Regulation of retinal differentiation in mammals is not adequately understood. Using single-cell RNA sequencing of control and Six3 and Six6 compound-mutant mouse embryonic eye-cups, we identified cell clusters and developmental trajectories jointly regulated by transcription factor Six3 and its close paralog Six6. In control retinas, naïve retinal progenitor cells had two major trajectories leading to ciliary margin cells and retinal neurons, respectively. The ciliary margin trajectory was directly from naïve retinal progenitor cells at G1 phase whereas the neuronal trajectory was through a neurogenic state marked by Atoh7 expression. Upon Six3 and Six6 dual deficiencies, both naïve and neurogenic retinal progenitors were defective, ciliary margin differentiation was enhanced, and multi-lineage neuronal differentiation was disrupted. An ectopic neuronal trajectory lacking the Atoh7+ state led to ectopic neurons. Additionally, opposing gradients of Wnt and Fgf signaling were perturbed. Our findings provide deeper insight into molecular mechanisms underlying early retinal differentiation in mammals.

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Single cell analyses reveal the transient emergence of retinal progenitor cells in the ciliary margin zone during human retinal development [Spatial]

Project description:Retina is the innermost, light-sensitive layer that lines the back of the eye and is vital for light sensing and image processing. All the retinal cells types are derived from retinal progenitor cells (RPCs) in an orderly spatio-temporal manner that has been well studied in vertebrates. To better understand the emergence of RPCs, their localisation and differentiation to retinal lineages, we performed single cell (sc) RNA-Seq of 24 samples spanning 13 time points from 10-21 post-conception weeks of human development. Several types of progenitors were identified, including early and late RPCs which in turn gave rise the transient neurogenic progenitors that differentiated to all retinal neurones. Spatial transcriptomic analyses combined with scRNA-Seq revealed localisation of early RPCs in the ciliary margin of developing human retinas up to 10 PCW of development and propagation of neural retina differentiation from the centre to the periphery. Single cell ATAC-Seq analyses of 11 samples spanning 8-21 PCW of human development identified Hippo-Yap signalling as key pathway regulating RPC proliferation and cell cycle exit. These results provide the molecular map of human retinal development which may help guide generation of RPCs from human pluripotent stem cells and the design of cell-based replacement therapies for treating retinal dystrophies

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Single cell analyses reveal the transient emergence of retinal progenitor cells in the ciliary margin zone during human retinal development [ATAC]

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Single cell analyses reveal the transient emergence of retinal progenitor cells in the ciliary margin zone during human retinal development [scRNA-seq]

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Single cell analyses reveal the transient emergence of retinal progenitor cells in the ciliary margin zone during human retinal development

Project description:Single cell analyses reveal the transient emergence of retinal progenitor cells in the ciliary margin zone during human retinal development

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Project description:Single cell analyses reveal the transient emergence of retinal progenitor cells in the ciliary margin zone during human retinal development [ATAC]

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A single-cell transcriptomic atlas of the human ciliary body

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Single cell analyses reveal the transient emergence of retinal progenitor cells in the ciliary margin zone during human retinal development [scRNA-seq]

Project description:Single cell analyses reveal the transient emergence of retinal progenitor cells in the ciliary margin zone during human retinal development [scRNA-seq]

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