Reprogramming to recover youthful epigenetic information and restore vision
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PROVIDER: PRJNA614634 | ENA |
REPOSITORIES: ENA
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Project description:Reprogramming to recover youthful epigenetic information and restore vision
| PRJNA655981 | ENA
Project description:Epigenetic reprogramming via a combination of three Yamanaka factors, Oct4, Sox2, and Klf4 (OSK), provides an effective way to promote axon regeneration in chemical- or injury-damaged neurons and improve neuronal function in aged mice. DNA methylation landscape is remodeled during this reprogramming process. This study was designed to examine DNA methylation age in differentiated human neurons post axonal damage with or without OSK expression. Differentiated SH-SY5Y neurons were transduced with AAV.DJ vectors to induce OSK expression for five days, followed by 24-hr treatment with 100nM vincristine (VCS) to induce neurite degeneration. Neurons were harvested at either day 1 or day 9 after VCS treatment. The Illumina Infinium DNA methylation EPIC array was used to obtain DNA methylation profiles. The skin & blood clock from Horvath 2018 (PMID: 30048243 PMCID: PMC6075434) was used for DNA methylation age analysis.
2020-09-26 | GSE147436 | GEO
Project description:Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity1-3. Changes to DNA methylation patterns over time form the basis of ageing clocks4, but whether older individuals retain the information needed to restore these patterns-and, if so, whether this could improve tissue function-is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity5-7. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information-encoded in part by DNA methylation-that can be accessed to improve tissue function and promote regeneration in vivo.
| S-EPMC7752134 | biostudies-literature
Project description:The restoration of light response with complex spatiotemporal features in retinal degenerative diseases towards retinal prosthesis has proven to be a considerable challenge over the past decades. Herein, inspired by the structure and function of photoreceptors in retinas, we develop artificial photoreceptors based on gold nanoparticle-decorated titania nanowire arrays, for restoration of visual responses in the blind mice with degenerated photoreceptors. Green, blue and near UV light responses in the retinal ganglion cells (RGCs) are restored with a spatial resolution better than 100?µm. ON responses in RGCs are blocked by glutamatergic antagonists, suggesting functional preservation of the remaining retinal circuits. Moreover, neurons in the primary visual cortex respond to light after subretinal implant of nanowire arrays. Improvement in pupillary light reflex suggests the behavioral recovery of light sensitivity. Our study will shed light on the development of a new generation of optoelectronic toolkits for subretinal prosthetic devices.
| S-EPMC5840349 | biostudies-literature
Project description:The role of postnatal experience in sculpting cortical circuitry, while long appreciated, is poorly understood at the level of cell types. We explore this in the mouse primary visual cortex (V1) using single-nucleus RNA-sequencing, visual deprivation, genetics, and functional imaging. We find that vision selectively drives the specification of glutamatergic cell types in upper layers (L) (L2/3/4), while deeper-layer glutamatergic, GABAergic, and non-neuronal cell types are established prior to eye opening. L2/3 cell types form an experience-dependent spatial continuum defined by the graded expression of ~200 genes, including regulators of cell adhesion and synapse formation. One of these, Igsf9b, a vision-dependent gene encoding an inhibitory synaptic cell adhesion molecule, is required for the normal development of binocular responses in L2/3. In summary, vision preferentially regulates the development of upper-layer glutamatergic cell types through the regulation of cell type-specific gene expression programs.
2021-12-27 | GSE190940 | GEO
Project description:OSKM activation can restore age-associated features in vitro, and its cyclic transient expression can extend lifespan in progeroid mice. We found that a single period of transient OSKM activation in old mice reconfigures its transcriptome and methylome towards youthful profile
2022-03-07 | GSE155740 | GEO
Project description:Ocular regenerative therapies are on track to revolutionize treatment of numerous blinding disorders, including corneal disease, cataract, glaucoma, retinitis pigmentosa, and age-related macular degeneration. A variety of transplantable products, delivered as cell suspensions or as preformed 3D structures combining cells and natural or artificial substrates, are in the pipeline. Here we review the status of clinical and preclinical studies for stem cell-based repair, covering key eye tissues from front to back, from cornea to retina, and including bioengineering approaches that advance cell product manufacturing. While recognizing the challenges, we look forward to a deep portfolio of sight-restoring, stem cell-based medicine. VIDEO ABSTRACT.
| S-EPMC6492284 | biostudies-literature
Project description:The neurons that restore walking after paralysis
| PRJNA764235 | ENA
Project description:Transcriptional profiling of Drosophila during Listeria infection as they die and as they recover upon ampicillin treatment
2016-04-18 | GSE60985 | GEO
Project description:Our laboratory previously demonstrated that perivascular stem/stromal cells (CD146+ pericytes) can effectively recover muscle mass after a period of immobilization in young adult mice. However, cell-based therapies are problematic in aged mouse models due to lack of viability upon transplantation. Therefore, the purpose of this study was to develop a pericyte-based, cell-free strategy to recover muscle mass after disuse in aged mice. Single-cell RNA sequencing (scRNA-Seq) was performed on adult mouse skeletal muscle after two weeks of unilateral hindlimb immobilization, which revealed that muscle-resident pericytes uniquely upregulate the long noncoding RNA Malat1, a negative regulator of Nrf2, and fail to induce antioxidant gene expression in response to reactive oxygen species (ROS; H2O2). This information was used to guide the design of a strategy in which healthy donor pericytes were stimulated with ROS to produce small extracellular vesicles (EVs) that were subsequently transplanted into 4- and 24-26-month-old C57BL/6 mice after two weeks of unilateral hindlimb immobilization. H2O2-primed healthy muscle-derived pericytes produced EVs in culture that effectively reduced restored myofiber CSA in both adult (p=0.009) and aged (p=0.006) muscle after disuse. In contrast, unprimed pericyte-derived EVs did not influence myofiber size. Neither primed, nor unprimed EVs recovered capillary density, yet both stimulated collagen turnover. Healthy ROS-primed pericyte-derived small EVs effectively improve skeletal muscle recovery after immobilization, representing a novel cell-free approach to rebuild muscle mass in older adults after a period of disuse.
2022-09-28 | GSE185560 | GEO