Driving Neurogenesis in Neural Stem Cells with High Sensitivity Optogenetics

AbstractOptogenetic stimulation of neural stem cells (NSCs) enables their activity-dependent photo-modulation. This provides a spatio-temporal tool for studying activity-dependent neurogenesis and for regulating the differentiation of the transplanted NSCs. Currently, this is mainly driven by viral transfection of channelrhodopsin-2 (ChR2) gene, which requires high irradiance and complex in vivo/vitro stimulation systems. Additionally, despite the extensive application of optogenetics in neuroscience, the transcriptome-level changes induced by optogenetic stimulation of NSCs have not been elucidated yet. Here, we made transformed NSCs (SFO-NSCs) stably expressing one of the step-function opsin (SFO)-variants of chimeric channelrhodopsins, ChRFR(C167A), which is more sensitive to blue light than native ChR2, via a non-viral transfection system usingpiggyBac transposon. We set up a simple low-irradiance optical stimulation (OS)-incubation system that inducedc-fos mRNA expression, which is activity-dependent, in differentiating SFO-NSCs. More neuron-like SFO-NCSs, which had more elongated axons, were differentiated with daily OS than control cells without OS. This was accompanied by positive/negative changes in the transcriptome involved in axonal remodeling, synaptic plasticity, and microenvironment modulation with the up-regulation of several genes involved in the Ca2+-related functions. Our approach could be applied for stem cell transplantation studies in tissue with two str...
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research

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Conditions:   T-Cell Lymphoma;   Indolent B-Cell Lymphoma Interventions:   Drug: Duvelisib;   Procedure: Peripheral blood draw Sponsors:   Washington University School of Medicine;   Verastem, Inc. Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
This article summarizes a presentation by Jonathan Li, MD, MMSc, at the International Antiviral Society-USA (IAS-USA) continuing education program held in Atlanta, Georgia, in March 2019. PMID: 32224499 [PubMed - in process]
Source: Topics in antiviral medicine - Category: Infectious Diseases Tags: Top Antivir Med Source Type: research
There is an increasing demand for the expansion of functional human hematopoietic stem cells (hHSCs) for various clinical applications. Based on our primary screening of antioxidant small molecule compounds library, a small molecule compound C2968 (chrysin) was identificated to expand cord blood CD34+ cells in vitro. Then we further verified the optimum concentration and explored its effect on hHSCs phenotype and biological function. C2968 could significantly increase the proportion and absolute number of CD34+CD38−CD49f+ and CD34+CD38−CD45RA−CD90+ cells under 2.5 μM. Furthermore, the total number of c...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Contributors : Elizabeth Ostrander ; Grant A ChallenSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusEpigenetic modifying enzymes DNMT3A and TET2 are recurrently mutated in hematological disorders despite possessing opposing biochemical functions in the DNA methylation processes. Using conditional ablation, we show these contrasting genotypes result in different functional effects in hematopoietic stem cells (HSCs). Loss of Dnmt3a bestows enhanced self-renewal on HSCs in serial, competitive repopulation assays while Tet...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
Although heterogeneity is recognized within the murine satellite cell pool, a comprehensive understanding of distinct subpopulations and their functional relevance in human satellite cells is lacking. We used a combination of single cell RNA sequencing and flow cytometry to identify, distinguish, and physically separate novel subpopulations of human PAX7+ satellite cells (Hu-MuSCs) from normal muscles. We found that, although relatively homogeneous compared to activated satellite cells and committed progenitors, the Hu-MuSC pool contains clusters of transcriptionally distinct cells with consistency across human individuals...
Source: eLife - Category: Biomedical Science Tags: Human Biology and Medicine Stem Cells and Regenerative Medicine Source Type: research
Abstract To investigate the protective function of low-level laser irradiation (LLLI) against ionizing irradiation and explore the molecular mechanism of photomodulation of Nrf2 protein, the impact of LLLI (635 nm, 5.7 J/cm2) before 2 Gy gamma ray radiation of radio-sensitive tissue hematopoietic stem cells was evaluated. As a result, reduced levels of reactive oxygen species and increased expression of antioxidant enzymes were detected. Moreover, increased expression of Nrf2 was observed after LLLI, whereas brusatol pretreatment before LLLI abolished this effect. In vivo, transplantation of human umbilical cord m...
Source: Tissue and Cell - Category: Cytology Authors: Tags: Tissue Cell Source Type: research
A 34-year-old man with chronic myelogenous leukemia status post allogeneic hematopoietic stem cell transplant (HSCT) on tacrolimus for graft-vs-host disease prophylaxis, presented with a 1-week history of fevers and severe headaches. Brain magnetic resonance imaging (MRI) demonstrated numerous small focal lesions in the left basal ganglia and left temporal lobe with a ring pattern, as well  as a large lesion in the left occipital lobe with mild leptomeningeal enhancement (Figure 1). Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, and Toxoplasma gondii was detected by polymerase chain reaction (PCR).
Source: Mayo Clinic Proceedings - Category: Internal Medicine Authors: Tags: Medical image Source Type: research
Autologous induced pluripotent stem cells (iPSC)-based therapies are considered to be promising in the transplantation field, however their immunological potential is unclear. These therapies require expansion, reprogramming and differentiation of the cells in vitro. Mitochondrial (mt) DNA mutations can arise from those procedures and they have been considered to be involved in the rejection of the cells after transplantation. We therefore hypothesized that single nucleotide polymorphisms (SNPs) in the mtDNA can contribute to autologous and allogeneic graft immunoreactivity and we assessed their immunogenicity in transplantation.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: (28) Source Type: research
Pulmonary chronic graft versus host disease (GVHD) is one of the thoracic manifestations that can complicate allogeneic hematopoietic stem cell transplantation (HSCT) causing respiratory failure and death. Lung transplantation (LTx) often remains the only therapeutic option for progressive forms although it has been reported in a small number of patients worldwide.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: (1290) Source Type: research
Our hypothesis is that human adipose mesenchymal stem cell (MSC)-derived extracellular vesicle (EV) can be used as a delivery platform for microRNAs to effectively attenuate lung ischemia-reperfusion injury (IRI).
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: (341) Source Type: research
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