We report directed differentiaion of retinal precursors in vitro from mouse ES cells. Six3+ rostral brain progenitors are generated by culturing ES cells under serum-free suspension conditions (SFEB culture) in the presence of Wnt and Nodal antagonists (Dkk1 and LeftyA), and subsequently steered to differentiate into Rx+ cells (16%) by treatment with activin and serum. Consistent with the characteristics of early neural retinal precursors, the induced Rx+ cells coexpress Pax6 and the mitotic marker Ki67, but not Nestin. The ES cell-derived precursors efficiently generate cells with the photoreceptor phenotype (rhodopsin+, recoverin+) when cocultured with embryonic retinal cells. Furthermore, organotypic culture studies demonstrate the selective integration and survival of ES cell-derived cells with the photoreceptor phenotype (marker expression and morphology) in the outer nuclear layer of the retina. Taken together, ES cells treated with SFEB/Dkk1/LeftyA/serum/activin generate neural retinal precursors, which have the competence of photoreceptor differentiation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1183536 | PMC |
| http://dx.doi.org/10.1073/pnas.0500010102 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
The University of British Columbia, Vancouver, BC, Canada.
Background: An imbalance between the production and clearance of amyloid beta (Aß) has emerged as a major cause of sporadic Alzheimer's disease (AD). Retinal wholemount studies can identify cell-specific involvement in Aß clearance mechanisms which cannot be accomplished in the brain ex vivo.
Methods: Eye cross-sections of double transgenic (Tg, APP-PS1) and non-carrier sibling female mice (n = 16, 4 per group) at 3- and 9- month ages were probed with antibodies 6E10 (Aβ1-16 amino-acid residues, soluble and insoluble species), ionized calcium-binding adapter molecule 1 (IBA1, microglia/macrophage), glial fibrillary acidic protein (GFAP, astrocytes), glutamine synthetase (GS, Müller cells) and aquaporin-4 (AQP4, membrane water channel) using immunofluorescence.
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Southern California, San Diego, CA, USA.
Background: Individuals with Down Syndrome (DS) exhibit a unique aging profile and have early-onset Alzheimer's Disease (AD) due to a triplication of the amyloid precursor protein (APP) gene on chromosome 21.
Method: Here, we present a study of a 73-year-old non-Hispanic White female with DS who underwent extensive clinical assessments for several decades. She had a cognitive and functional impairment consistent with DS and AD-like symptoms.
In defence of ferroptosis.
Signal Transduct Target Ther
January 2025
The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
Rampant phospholipid peroxidation initiated by iron causes ferroptosis unless this is restrained by cellular defences. Ferroptosis is increasingly implicated in a host of diseases, and unlike other cell death programs the physiological initiation of ferroptosis is conceived to occur not by an endogenous executioner, but by the withdrawal of cellular guardians that otherwise constantly oppose ferroptosis induction. Here, we profile key ferroptotic defence strategies including iron regulation, phospholipid modulation and enzymes and metabolite systems: glutathione reductase (GR), Ferroptosis suppressor protein 1 (FSP1), NAD(P)H Quinone Dehydrogenase 1 (NQO1), Dihydrofolate reductase (DHFR), retinal reductases and retinal dehydrogenases (RDH) and thioredoxin reductases (TR).
View Article and Find Full Text PDFApolipoprotein E dysfunction in Alzheimer's disease: a study on miRNA regulation, glial markers, and amyloid pathology.
Front Aging Neurosci
December 2024
Department of Ophthalmology and Visual Sciences, Faculty of Medicine, Eye Care Centre, The University of British Columbia, Vancouver, BC, Canada.
Introduction: Apolipoprotein E (ApoE) plays a crucial role in lipid homeostasis, predominantly expressed in astrocytes and to a lesser extent in microglia within the central nervous system (CNS). While the allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), its precise role in AD pathogenesis remains elusive. -knockout (-ko) mice, mice expressing human , and human carriers exhibit similar deficits in lipid metabolism, cognitive and behavioral functions, and neurodegeneration.
View Article and Find Full Text PDFPurpose: Ambient light exposure is linked to myopia development in children and affects myopia susceptibility in animal models. Currently, it is unclear which signals mediate the effects of light on myopia. All- retinoic acid (atRA) and dopamine (DA) oppositely influence experimental myopia and may be involved in the retino-scleral signaling cascade underlying myopic eye growth.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!