Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Integrative Single-cell Transcriptomics and Single-cell Epigenomics Mapping the Developmental Dynamics of Fetal Retina

ABSTRACT: The underlying mechanisms that determine gene expression and chromatin accessibility in retinogenesis are poorly understood. Here, we performed scRNA-seq and scATAC-seq on human embryonic retina samples from 9 to 26 post-conceptional weeks, explored the heterogeneity of retinal progenitor cells (RPCs) and neurogenic RPCs (NPCs), and verified the differentiation trajectory from RPCs to seven major types of retinal cells. Additionally, we identified cell-lineage-determining transcription factors (TFs) and refined their gene regulatory networks (GRNs) at transcriptomic and epigenomic levels. The inhibitor of RE-1 silencing transcription factor (REST) on retinospheres was found to have led to more neurogenesis with regular arrangement, whereas a decrease of Müller glial cells was observed. We also described the classification of developing RPC-derived cells and their correlation with pathogenic genes of multiple ocular diseases. Overall, we provided a framework for integrated exploration of the developmental dynamics of the human primary retina at the single-cell resolution.

ORGANISM(S): Homo sapiens

PROVIDER: GSE228370 | GEO | 2023/03/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

MicroRNAs miR-25, let-7 and miR-124 regulate the neurogenic potential of Müller glia in mice [NanoString]

Project description:In order to identify the miRNAs in postnatal day 2 (P2) retinal progenitor cells (RPCs), and P8, P11, and adult Müller glia (MG) of the neural retina, we isolated the retinal progenitors from Sox2-CreER: Stopf/f-tdTomato and MG from Rlbp-CreER: Stopf/f-tdTomato mice by means of fluorescent activated cell sorting and analyzed their miRNAs using NanoStrings Technologies®. We next compared miRNA expression of RPCs with MG. We found that most specific miRNAs decline with glial maturation (RPC miRNAs) while others increase (MG miRNAs). Overexpression of miRNA-25 found in RPCs and inhibition of MG miRNA let-7 can induce a neurogenic potential in MG and initiates a de novo differentiation toward neuronal fates.

2019-08-14 | GSE135835 | GEO

Transcriptome and DNA methylome of mouse Müller glia

Project description:Müller cells are the primary glia of the neural retina and play crucial roles in maintaining the structural and functional homeostasis of the retina. Müller cells also possess certain levels of retinal regeneration capacity, especially in lower vertebrates. In this study, we deep sequenced the transcriptomes and methylomes of mouse Müller cells and early retinal progenitor cells (RPCs), as well as Müller cells from injured retinas and aged retinas, which will help to reveal molecular mechanisms governing Müller cells development, physiological functions and regeneration activities.

2019-11-12 | GSE124532 | GEO

Gene expression profiling of developing murine Müller glia

Project description:To study molecular changes during differentiation of retinal progenitor cells (RPCs) into Müller glia, we isolated Notch1+ cells (Notch1 is a marker of RPCs) from postnatal-day (P) 0, 3, 7, and 14 retinas,as well as Glast + cells (Glast/Slc1a3 is a marker of Müller glia precursors and Müller glia in the retina) from P7, P14, P21, and P28 retinas. We studied gene expression in these cells using MEEBO microarrays.

2019-07-23 | GSE122301 | GEO

MicroRNAs miR-25, let-7 and miR-124 regulate the neurogenic potential of Müller glia in mice [RNA-Seq]

Project description:Müller glial cells (MG) generate retinal progenitor (RPC)-like cells after injury in non-mammalian species, though this does not occur in the mammalian retina. Studies have profiled gene expression in these cells to define genes that may be relevant to their differences in neurogenic potential. However, less is known about differences in micro-RNA (miRNA) expression. In this study, we compared miRNAs from RPCs and MG to identify miRNAs more highly expressed in RPCs, and others more highly expressed in MG. To determine whether these miRNAs are relevant to the difference in neurogenic potential between these two cell types, we tested them in dissociated cultures of MG using either mimics or antagomiRs to increase or reduce expression, respectively. Among the miRNAs tested, miR-25 and miR-124 over-expression, or let-7 antagonism, induced Ascl1 expression and conversion of approximately 40% of mature MG into a neuronal/RPC phenotype. Our results suggest that the differences in miRNA expression between MG and RPCs contribute to their difference in neurogenic potential and that manipulations in miRNAs provide a new tool to reprogram MG for retinal regeneration.

2019-08-14 | GSE135816 | GEO

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

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 [ATAC]

2023-11-29 | GSE234003 | GEO

Identification of differential expressed genes among P-RPC, rESC-RPC1 and rESC-RPC2 through genome-wide transcript profiling

Project description:Degenerative retinal diseases like age-related macular degeneration (AMD) are the leading cause of blindness. Cell transplantation showed promising therapeutic effect for such diseases, and retinal progenitor cell (RPC) derived from embryonic stem cell (ESC) is one of the sources of such donor cells. Here, we established two protocols through which two types of rat ESC-derived RPCs (rESC-RPCs) were obtained and both contained some NPCs and committed retina lineage cells. As P-RPCs have been reported to successfully integrate into host eyes, we sough to identify differentially expressed genes among P-RPCs, rESC-RPC1s and rESC-RPC2s through genome-wide transcript profiling. rESC-RPC2 can integrate into the host retina, form synaptic connections and restore visual function after transplanted into the degenerative retinal disease model RCS rat.

2015-10-01 | GSE67213 | 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

Bankable human iPSC-derived Retinal Progenitors as a New Source of Multipotent Cells

Project description:Retinal progenitor cells (RPCs) are the source of all retinal cell types during retinogenesis. Until now, the isolation and expansion of RPCs has been at the expense of their multipotency. Here, we report simple methods and media for the generation, expansion, and cryopreservation of human induced pluripotent stem-cell derived-RPCs (hiRPCs). Thawed and passed hiRPCs maintained biochemical and transcriptional RPC phenotypes and their ability to differentiate into all retinal cell types. Specific conditions allowed the generation of large cultures of photoreceptor precursors enriched up to 90% within a few weeks and without a purification step. Combined RNA-seq analysis between hiRPCs and retinal organoids identified genes involved in developmental or degenerative retinal diseases. Thus, hiRPC lines could provide a new source of retinal cells for cell-based therapies or drug discovery and could be an advanced cellular tool to better understand retinal dystrophies.

2023-08-08 | GSE220792 | GEO

Single-cell RNA-seq reveals the molecular progression of retinal progenitors in human embryonic stem cell models of early retinogenesis

Project description:We used single-cell RNA-sequencing (scRNA-seq) on human embryonic stem cell (hESC)-derived retinal organoid to deconstruct RPC developmental trajectory in the early retinogenesis, which revealed the fate branchpoint in RPC progression.

2019-08-22 | GSE122783 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data