A5039589277- Retinal Development and Disorders
- Retinal Diseases and Treatments
- CRISPR and Genetic Engineering
- Corneal surgery and disorders
- Cellular transport and secretion
- Ocular Surface and Contact Lens
- RNA regulation and disease
- Corneal Surgery and Treatments
- Single-cell and spatial transcriptomics
- Ubiquitin and proteasome pathways
- Complement system in diseases
- Photochromic and Fluorescence Chemistry
- Reproductive Biology and Fertility
- Receptor Mechanisms and Signaling
- bioluminescence and chemiluminescence research
- RNA Research and Splicing
- Virus-based gene therapy research
- Energy Harvesting in Wireless Networks
- Pluripotent Stem Cells Research
- Autophagy in Disease and Therapy
- Photoreceptor and optogenetics research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neonatal Respiratory Health Research
- Tissue Engineering and Regenerative Medicine
Newcastle University
2020-2024
Centre for Life
2021
Centro Andaluz de Biología Molecular y Medicina Regenerativa
2019
Single cell (sc) analyses of key embryonic, fetal and adult stages were performed to generate a comprehensive single atlas all the corneal adjacent conjunctival types from development adulthood. Four human seventeen embryonic corneas 10 21 post conception week (PCW) specimens dissociated cells subjected scRNA- and/or ATAC-Seq using 10x Genomics platform. These embedded Uniform Manifold Approximation Projection (UMAP) clustered Seurat graph-based clustering. Cluster identification was based...
Molecular information on the early stages of human retinal development remains scarce due to limitations in obtaining eye samples. Pluripotent stem cell-derived organoids (ROs) provide an unprecedented opportunity for studying retinogenesis. Using a combination single cell RNA-seq and spatial transcriptomics we present first-time spatiotemporal transcriptome RO development. Our data demonstrate that ROs recapitulate key events retinogenesis including optic vesicle/cup formation, presence...
Retinal drug toxicity screening is essential for the development of safe treatment strategies a large number diseases. To this end, retinal organoids derived from human pluripotent stem cells (hPSCs) provide suitable platform due to their similarity retina and ease generation in large-scale formats. In study, two hPSC cell lines were differentiated organoids, which comprised all key types multiple nuclear synaptic layers. Single-cell RNA-Seq indicated maintenance ganglion bipolar cells: both...
Abstract Microglia are the primary resident immune cells in retina. They regulate neuronal survival and synaptic pruning making them essential for normal development. Following injury, they mediate adaptive responses under pathological conditions can trigger neurodegeneration exacerbating effect of a disease. Retinal organoids derived from human induced pluripotent stem (hiPSCs) increasingly being used range applications, including disease modelling, development new therapies study...
Abstract Age-related macular degeneration (AMD) is a multifactorial disease, which characterized by loss of central vision, affecting one in three people the age 75. The Y402H polymorphism complement factor H (CFH) gene significantly increases risk AMD. We show that Y402H-AMD-patient-specific retinal pigment epithelium (RPE) cells are significant reduction number melanosomes, an increased swollen lysosome-like-vesicles with fragile membranes, Cathepsin D leakage into drusen-like deposits and...
Abstract As one of the primary points entry xenobiotic substances and infectious agents into body, lungs are subject to a range dysfunctions diseases that together account for significant number patient deaths. In view this, there is an outstanding need in vitro systems which assess impact both lungs. To address this issue, we have developed protocol generate airway epithelial basal-like cells from induced pluripotent stem cells, simplifies manufacture cellular models human upper airways....
Abstract The carboxy-terminus of the spliceosomal protein PRPF8 , which regulates RNA helicase Brr2, is a hotspot for mutations causing retinitis pigmentosa-type 13, with unclear role in human splicing and tissue-specificity mechanism. We used patient induced pluripotent stem cells-derived cells, carrying heterozygous c.6926 A > C (p.H2309P) mutation to demonstrate retinal-specific endophenotypes comprising photoreceptor loss, apical-basal polarity ciliary defects. Comprehensive...
Abstract Introduction Mutations in pre‐mRNA processing factor 31 ( PRPF31 ), a core protein of the spliceosomal tri‐snRNP complex, cause autosomal‐dominant retinitis pigmentosa (adRP). It has remained an enigma why mutations ubiquitously expressed proteins result retina‐specific disorders, and so far, underlying mechanism splicing factors‐related RP is poorly understood. Methods We used induced pluripotent stem cell (iPSC) technology to generate retinal organoids RPE models from four...
Development of the retina is regulated by growth factors, such as insulin-like factors 1 and 2 (IGF-1/2), which coordinate proliferation, differentiation, maturation neuroepithelial precursors cells. In circulation, IGF-1/2 are transported insulin factor binding proteins (IGFBPs) family members. IGFBPs can impact positively negatively on IGF-1, making it available or sequestering IGF-1 to from its receptor. this study, we investigated expression their role in generation human retinal...
Abstract Molecular information on the early stages of human retinal development remains scarce due to limitations in obtaining eye samples. Pluripotent stem cell-derived organoids provide an unprecedented opportunity for studying retinogenesis. Using a combination single cell RNA-Seq and spatial transcriptomics we present first-time spatio-temporal transcriptome organoid development. Our data demonstrate that recapitulate key events retinogenesis including optic vesicle/cup formation,...
Summary To study the development and composition of human ocular surface, we performed single cell (sc) RNA-Seq at key embryonic, fetal adult stages generated first atlas corneal types from to adulthood. Our data indicate that during development, conjunctival epithelium is be specified surface epithelium, followed by establishment proliferative epithelial progenitors, which predate formation limbal niche a few weeks. Bioinformatic comparison clusters identified GPHA2, novel cell-surface...
<title>Abstract</title> <bold>Conclusions:</bold> Importantly, the use of retinal organoids provides a valuable platform to study AS and unravel disease mechanisms in more physiologically relevant context, opening avenues for further research potential therapeutic interventions. Together our data indicate that cones may be sensitive <italic>PROM1 </italic>exon 4 skipping, corroborating pathogenesis late-onset mild maculopathy. <bold>Introduction: </bold>Alternative splicing (AS) is crucial...
PRPF31 gene codes for a ubiquitously expressed splicing factor but mutations affect exclusively the retina, producing progressive death of photoreceptor cells. We have identified novel mutation in patient with autosomal dominant retinitis pigmentosa. A blood sample was obtained and mononuclear cells were reprogrammed using non-integrative Sendai virus to generate cell line CABi001-A. The iPSC has been characterized pluripotency differentiation capacity will be differentiated toward...
Abstract Mutations in pre-mRNA processing factor 31 (PRPF31), a core protein of the spliceosomal tri-snRNP complex, cause autosomal-dominant retinitis pigmentosa (adRP). It has remained an enigma why mutations ubiquitously expressed proteins result retina-specific disorders, and so far, underlying mechanism splicing factors-related RP is poorly understood. Here, we used iPSC technology to generate retinal organoids RPE models from three patients with severe very PRPF31-adRP, normal...