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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234971 | GEO | 2023/11/29

REPOSITORIES: GEO

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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]

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

2023-11-29 | GSE234003 | GEO

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

2023-11-29 | GSE234035 | GEO

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

2023-11-29 | GSE234963 | GEO

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

| PRJNA983813 | ENA

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

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

| PRJNA979192 | ENA

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

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

| PRJNA979220 | ENA

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]

| PRJNA983820 | ENA

The Ciliary Margin Zone of the Mammalian Retina Generates Retinal Ganglion Cells.

Project description:The retina of lower vertebrates grows continuously by integrating new neurons generated from progenitors in the ciliary margin zone (CMZ). Whether the mammalian CMZ provides the neural retina with retinal cells is controversial. Live imaging of embryonic retina expressing eGFP in the CMZ shows that cells migrate laterally from the CMZ to the neural retina where differentiated retinal ganglion cells (RGCs) reside. Because Cyclin D2, a cell-cycle regulator, is enriched in ventral CMZ, we analyzed Cyclin D2-/- mice to test whether the CMZ is a source of retinal cells. Neurogenesis is diminished in Cyclin D2 mutants, leading to a reduction of RGCs in the ventral retina. In line with these findings, in the albino retina, the decreased production of ipsilateral RGCs is correlated with fewer Cyclin D2+ cells. Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity.

| S-EPMC5234854 | biostudies-literature

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

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

Project description:In albinism, aberrations in the ipsi-/contralateral retinal ganglion cell (RGC) ratio compromise the functional integrity of the binocular circuit. Here, we focus on the mouse ciliary margin zone (CMZ), a neurogenic niche at the embryonic peripheral retina, to investigate developmental processes regulating RGC neurogenesis and identity acquisition. We found that the mouse ventral CMZ generates predominantly ipsilaterally projecting RGCs, but this output is altered in the albino visual system because of CyclinD2 downregulation and disturbed timing of the cell cycle. Consequently, albino as well as CyclinD2-deficient pigmented mice exhibit diminished ipsilateral retinogeniculate projection and poor depth perception. In albino mice, pharmacological stimulation of calcium channels, known to upregulate CyclinD2 in other cell types, augmented CyclinD2-dependent neurogenesis of ipsilateral RGCs and improved stereopsis. Together, these results implicate CMZ neurogenesis and its regulators as critical for the formation and function of the mammalian binocular circuit.

| S-EPMC9822872 | biostudies-literature

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