A5039701907- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- 3D Printing in Biomedical Research
- CRISPR and Genetic Engineering
- Neuroscience and Neuropharmacology Research
- Molecular Biology Techniques and Applications
- Renal and related cancers
- Epigenetics and DNA Methylation
- Hormonal and reproductive studies
- Neuropeptides and Animal Physiology
- Neuroscience and Neural Engineering
- Retinal Imaging and Analysis
- Advanced Proteomics Techniques and Applications
- Mesenchymal stem cell research
- Retinal Diseases and Treatments
- Single-cell and spatial transcriptomics
- Retinal Development and Disorders
- Gene expression and cancer classification
- Cancer, Stress, Anesthesia, and Immune Response
- Receptor Mechanisms and Signaling
- RNA Interference and Gene Delivery
- Pain Mechanisms and Treatments
- Microfluidic and Bio-sensing Technologies
- Axon Guidance and Neuronal Signaling
- Stress Responses and Cortisol
National Institutes of Health
2016-2024
National Center for Advancing Translational Sciences
2016-2024
Government of the United States of America
2022
Sanford Burnham Prebys Medical Discovery Institute
2006-2016
Discovery Institute
2016
University of Freiburg
1999-2015
University of California, San Diego
2007
Essentially all knowledge about adult hippocampal neurogenesis in humans still comes from one seminal study by Eriksson et al. 1998, although several others have provided suggestive findings. But only little information has been available how far the situation animal models would reflect conditions and aging human brain. We therefore here mapped numerous features associated with rodents samples hippocampus across entire lifespan. Such data not offer proof of humans, because it is based on...
Development of new non-addictive analgesics requires advanced strategies to differentiate human pluripotent stem cells (hPSCs) into relevant cell types. Following principles developmental biology and translational applicability, here we developed an efficient stepwise differentiation method for peptidergic non-peptidergic nociceptors. By modulating specific signaling pathways, hPSCs were first converted SOX10
Efficient translation of human induced pluripotent stem cells (hiPSCs) requires scalable cell manufacturing strategies for optimal self-renewal and functional differentiation. Traditional manual culture is variable labor intensive, posing challenges high-throughput applications. Here, we established a robotic platform automated all essential steps hiPSC differentiation under chemically defined conditions. This approach allowed rapid standardized billions hiPSCs that can be produced in...
Human gliogenesis remains poorly understood, and derivation of astrocytes from human pluripotent stem cells (hPSCs) is inefficient cumbersome. Here, we report controlled glial differentiation hPSCs that bypasses neurogenesis, which otherwise precedes astrogliogenesis during brain development in vitro differentiation. were first differentiated into radial (RGCs) resembling resident RGCs the fetal telencephalon, modulation specific cell signaling pathways resulted direct stepwise induction key...
Phenotypic screens using human induced pluripotent stem cell–derived nociceptors hold promise for the development of better analgesics.
To determine whether transcriptional reprogramming is capable of reversing the developmental aging normal human somatic cells to an embryonic state.An isogenic system was utilized facilitate accurate assessment telomere restriction fragment (TRF) length aged differentiated that stem (hES) cell line from which they were originally derived. An hES-derived mortal clonal strain EN13 reprogrammed by SOX2, OCT4 and KLF4. The six resulting induced pluripotent (iPS) lines surveyed for length,...
With concurrent global epidemics of chronic pain and opioid use disorders, there is a critical need to identify, target manipulate specific cell populations expressing the mu-opioid receptor (MOR). However, available tools transgenic models for gaining long-term genetic access MOR+ neural types circuits involved in modulating pain, analgesia addiction across species are limited. To address this, we developed catalog MOR promoter (MORp) based constructs packaged into adeno-associated viral...
As a substrate of protein kinase C (PKC), neurogranin (NG) is involved in the regulation calcium signaling and activity-dependent plasticity. Recently, we have shown that, rodent cerebellum, NG exclusively expressed by gamma-aminobutyric acidergic Golgi cells, whereas, monkey brush cells were only neuronal population expressing (Singec et al. [2003] J. Comp. Neurol. 459:278-289). In present study, analyzed neocortical hippocampal expression patterns adult mouse (C57Bl/6), rat (Wistar),...
Abstract In the hippocampus, synaptic vesicle protein synaptoporin (SPO) has been reported to be exclusively enriched in granule cell axons, mossy fibers. this study, we show that adult rats and mice SPO immunoreactivity (IR) is also detectable strata oriens, radiatum, lacunosum‐moleculare of CA1–CA3, as well perisomatically hippocampus proper fascia dentata. situ hybridization confirmed mRNA was present cells CA3 pyramidal but not CA1 cells. Importantly, scattered throughout hippocampal...
Abstract Neurogranin (NG) is a brain‐specific protein kinase C substrate involved in the regulation of calcium signaling and neuronal plasticity. A rostrocaudal expression profile, with large amounts telencephalic brain regions low levels phylogenetically older structures, was reported previously. In cerebellum, NG has not been described. By using immunocytochemistry situ hybridization, we found that expressed mouse (C57Bl/6), rat (Wistar), monkey ( Cercopithecus aetiops ) cerebella. Golgi...
Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, determined proteomic phosphoproteomic profiles hESCs their specified multipotent derivatives (hNSCs). This quantitative dataset (nearly 13,000 proteins 60,000 phosphorylation sites) provides unique molecular insights into pluripotency lineage entry....
Many cytochrome P450 (P450) isoforms are selectively inducible by xenobiotics, e.g. pharmaceuticals like the anti‐epileptic drug phenytoin. Some of these enzymes involved in metabolism gonadal hormones and great importance, especially early brain development. In this study, hydroxylation testosterone rat microsomes from control phenytoin‐induced animals was examined use high performance liquid chromotography (HPLC) provided with a photodiode array detector (PDA). rats, is converted...
Human fetal neural stem/progenitor cells (hNSCs) are investigated for their potential as a cell source cell-based therapies in neurodegenerative diseases. However, the limited availability of tissue and insufficient understanding lineage-dependent pattern survival, migration, differentiation following engraftment still unresolved issues. In current study hNSCs derived from different brain regions were long-term expanded vitro to yield proliferating neurospheres giving rise neurons, astro-,...
N-glycosylation mediates many biological functions. Genetic defects in the pathway cause >35 inherited human disorders called congenital of glycosylation (CDGs). As a result, some sites are unoccupied. Serum transferrin is diagnostic marker for these patients, but there no corresponding cellular markers to assess competence. Therefore, we engineered green fluorescent protein (GFP) construct measure site occupancy. We designed an endoplasmic reticulum-retained GFP biomarker whose fluorescence...
SEQUIN is a web-based application (app) that allows fast and intuitive analysis of RNA sequencing data derived for model organisms, tissues, single cells. Integrated app functions enable uploading datasets, quality control, gene set enrichment, visualization, differential expression analysis. We also developed the iPSC Profiler, practical module scoring tool helps measure compare pluripotent differentiated cell types. Benchmarking to other commercial non-commercial products underscored...
The proteosome inhibitor bortezomib has revolutionized the treatment of multiple hematologic malignancies, but in many cases, its efficacy is limited by a dose-dependent peripheral neuropathy. We show that human induced pluripotent stem cell (hiPSC)-derived motor neurons and sensory provide model system for study bortezomib-induced neuropathy, with promising implications furthering mechanistic understanding developing treatments preventing axonal damage. Human tissue culture displayed...