A5003360721- Retinal Development and Disorders
- Neurogenesis and neuroplasticity mechanisms
- Developmental Biology and Gene Regulation
- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- Zebrafish Biomedical Research Applications
- Axon Guidance and Neuronal Signaling
- Pluripotent Stem Cells Research
- Photochromic and Fluorescence Chemistry
- CRISPR and Genetic Engineering
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
- Nerve injury and regeneration
- RNA regulation and disease
- Retinal Diseases and Treatments
- Ocular Disorders and Treatments
- MicroRNA in disease regulation
- Retinoids in leukemia and cellular processes
- Hearing, Cochlea, Tinnitus, Genetics
- Neurobiology and Insect Physiology Research
- Corneal Surgery and Treatments
- Cell Adhesion Molecules Research
- Glaucoma and retinal disorders
- interferon and immune responses
University of Washington
2016-2025
Institute for Stem Cell Biology and Regenerative Medicine
2025
Thomas University
2023
Seattle University
2002-2017
Bremen Institute for Applied Beam Technology
2014
California Institute for Regenerative Medicine
2010
Philipps University of Marburg
2010
Neurological Surgery
2005
Cleveland Clinic
2003
Friedrich Schiller University Jena
1995
The laboratory mouse shares the majority of its protein-coding genes with humans, making it premier model organism in biomedical research, yet two mammals differ significant ways. To gain greater insights into both shared and species-specific transcriptional cellular regulatory programs mouse, Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications replication domains throughout genome diverse cell tissue types. By...
The retina is subject to degenerative conditions, leading blindness. Although retinal regeneration robust in lower vertebrates, does not occur the adult mammalian retina. Thus, we have developed efficient methods for deriving neurons from human embryonic stem (hES) cells. Under appropriate culture up 80% of H1 line can be directed progenitor fate, and express a gene expression profile similar progenitors derived fetal hES cell-derived differentiate primarily into inner (ganglion amacrine...
Background Inherited and acquired retinal degenerations are frequent causes of visual impairment photoreceptor cell replacement therapy may restore function to these individuals. To provide a source new neurons for based therapies, we developed methods derive progenitors from human ES cells. Methodology/Physical Findings In this report have used similar method direct induced pluripotent stem cells (iPS) fibroblasts progenitor fate, competent generate photoreceptors. We also found could...
Müller glia can serve as a source of new neurons after retinal damage in both fish and birds. Investigations regeneration the mammalian retina vitro have provided some evidence that proliferate generate rods; however, this occurs vivo is not conclusive. We investigated whether potential to mouse by eliminating ganglion amacrine cells with intraocular NMDA injections stimulating glial re-enter mitotic cycle treatment specific growth factors. The proliferating dedifferentiate subset these...
To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, systematically compared these with human DHS maps from orthologous compartments. We found that genomes have undergone extensive cis-regulatory rewiring combines branch-specific innovation loss widespread repurposing conserved DHSs to alternative fates, this process is mediated by turnover transcription factor (TF) recognition...
Significance The retina is subject to a variety of insults that lead degeneration one or more types neurons and ultimate visual impairment blindness. Although the retinas nonmammalian vertebrates can regenerate new after injury, mammalian largely lack this potential. We have tested whether expression proneural transcription factor Ascl1 may be key difference between fish mouse by targeting cells provide retinal progenitors in mature retina, Müller glia. Our results show at least differences...
Highlights•scRNA-seq of human retina highlights key developmental transition states•hPSC-derived retinal organoids mimic fetal cellular composition•Inner layers in exhibit differences gene expression and organization•Fetal cultures resemble but maintain better inner laminationSummaryTo study the development retina, we use single-cell RNA sequencing (RNA-seq) at stages follow major cell types as well populations transitional cells. We also analyze stem (hPSC)-derived organoids; although have...
Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia (MG) that activate the gene encoding proneural factor Achaete-scute homolog 1 (Ascl1; also known as Mash1 in mammals) and de-differentiate into progenitor cells. By contrast, mammalian MG limited regenerative response fail upregulate Ascl1 after injury. To test whether ASCL1 could restore neurogenic potential MG, we overexpressed dissociated mouse cultures intact explants. ASCL1-infected...
The basic body plan and major physiological axes have been highly conserved during mammalian evolution, yet only a small fraction of the human genome sequence appears to be subject evolutionary constraint. To quantify cis- versus trans-acting contributions regulatory we performed genomic DNase I footprinting mouse across 25 cell tissue types, collectively defining ∼8.6 million transcription factor (TF) occupancy sites at nucleotide resolution. Here show that TF footprints conjointly encode...
Significance The sequential generation of different types neurons and glia is a fundamental property neurogenesis, but little known about the mechanisms controlling this phenomenon. Conditional deletion Dicer prevents progenitors from progressing in their competence to generate late cell types, indefinitely generating early types. We now elucidate molecular mechanism for Three microRNAs, let-7, microRNA-125, microRNA-9, serve as key regulators developmental transition retinal progenitors....
Regenerative neuroscience aims to stimulate endogenous repair in the nervous system replace neurons lost from degenerative diseases. Recently, we reported that overexpressing transcription factor Ascl1 Müller glia (MG) is sufficient MG regenerate functional adult mouse retina. However, this process inefficient, and only a third of Ascl1-expressing generate new neurons. Here, test whether proneural factors Atoh1/7 class can further promote regenerative capacity MG. We find combination...
We previously used single-cell transcriptomic analysis to characterize human fetal retinal development and assessed the degree which organoids recapitulate normal development. now extend analyses incorporate assay for transposase-accessible chromatin sequencing (scATAC-seq), a powerful method potential gene regulatory networks through changes in accessible that accompany cell-state changes. The combination of scATAC-seq RNA (scRNA-seq) provides view developing retina at an unprecedented...
ABSTRACT The vertebrate eye develops from the neuroepithelium of ventral forebrain by evagination and formation optic vesicle. Classical embryological studies have shown that surrounding extraocular tissues – surface ectoderm mesenchyme are necessary for normal growth differentiation. We used explant cultures chick vesicles to study regulation retinal pigmented epithelium (RPE) patterning differentiation during early development. Our results show is required induction maintenance expression...
The results of several recent studies have demonstrated that cell commitment and differentiation in the developing vertebrate retina are influenced by cell-cell interactions within microenvironment. Retinoic acid has been shown to influence fates during development nervous system, retinoic detected embryonic retina. To determine whether mediates specific neuronal phenotypes retinal histogenesis, we treated dissociated cultures neonatal rat with varying concentrations all-trans or 9-cis...
Abstract Growing evidence suggests that glial cells may have a role as neural precursors in the adult central nervous system. Although it has been shown Müller exhibit progenitor characteristics postnatal chick and rat retinae, their progenitor-like developed human retina is unknown. We first reported of spontaneously immortalized cell line MIO-M1, but recently we derived similar lines from several eye donors. Since immortalization one main properties stem cells, investigated whether these...
Most mammals have two types of cone photoreceptors, which contain either medium wavelength (M) or short (S) opsin. The number and spatial organization varies dramatically among species, presumably to fine-tune the retina for different visual environments. In mouse, S- M-opsin are expressed in an opposing dorsal-ventral gradient. We previously reported that opsin patterning requires thyroid hormone beta2, a nuclear receptor regulates transcription conjunction with its ligand, (TH). Here we...