Browsing by Subject "differentiation"

Now showing 1 - 10 of 13
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    Addressing Diverse Needs: Differentiation in Distance Learning
    (2009) Lamb, Annette; Johnson, Larry
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    Carbon nanotube multilayered nanocomposites as multifunctional substrates for actuating neuronal differentiation and functions of neural stem cells
    (Elsevier, 2018-08) Shao, Han; Li, Tingting; Zhu, Rong; Xu, Xiaoting; Yu, Jiandong; Chen, Shengfeng; Song, Li; Ramakrishna, Seeram; Lei, Zhigang; Ruan, Yiwen; He, Liumin; Anatomy and Cell Biology, School of Medicine
    Carbon nanotubes (CNTs) have shown potential applications in neuroscience as growth substrates owing to their numerous unique properties. However, a key concern in the fabrication of homogeneous composites is the serious aggregation of CNTs during incorporation into the biomaterial matrix. Moreover, the regulation mechanism of CNT-based substrates on neural differentiation remains unclear. Here, a novel strategy was introduced for the construction of CNT nanocomposites via layer-by-layer assembly of negatively charged multi-walled CNTs and positively charged poly(dimethyldiallylammonium chloride). Results demonstrated that the CNT-multilayered nanocomposites provided a potent regulatory signal over neural stem cells (NSCs), including cell adhesion, viability, differentiation, neurite outgrowth, and electrophysiological maturation of NSC-derived neurons. Importantly, the dynamic molecular mechanisms in the NSC differentiation involved the integrin-mediated interactions between NSCs and CNT multilayers, thereby activating focal adhesion kinase, subsequently triggering downstream signaling events to regulate neuronal differentiation and synapse formation. This study provided insights for future applications of CNT-multilayered nanomaterials in neural fields as potent modulators of stem cell behavior.
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    Chapter Six - Molecular signaling in bone cells: Regulation of cell differentiation and survival
    (Elsevier, 2019-02-04) Plotkin, Lilian I.; Bruzzaniti, Angela; Biomedical Sciences and Comprehensive Care, School of Dentistry
    The achievement of proper bone mass and architecture, and their maintenance throughout life requires the concerted actions of osteoblasts, the bone forming cells, and osteoclasts, the bone resorbing cells. The differentiation and activity of osteoblasts and osteoclasts are regulated by molecules produced by matrix-embedded osteocytes, as well as by cross-talk between osteoblasts and osteoclasts through secreted factors. In addition, it is likely that direct contact between osteoblast and osteoclast precursors, and the contact of these cells with osteocytes and cells in the bone marrow, also modulate bone cell differentiation and function. With the advancement of molecular and genetic tools, our comprehension of the intracellular signals activated in bone cells has evolved significantly, from early suggestions that osteoblasts and osteoclasts have common precursors and that osteocytes are inert cells in the bone matrix, to the very sophisticated understanding of a network of receptors, ligands, intracellular kinases/phosphatases, transcription factors, and cell-specific genes that are known today. These advances have allowed the design and FDA-approval of new therapies to preserve and increase bone mass and strength in a wide variety of pathological conditions, improving bone health from early childhood to the elderly. We have summarized here the current knowledge on selected intracellular signal pathways activated in osteoblasts, osteocytes, and osteoclasts.
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    Cracd Marks the First Wave of Meiosis during Spermatogenesis and Is Mis-Expressed in Azoospermia Mice
    (MDPI, 2020-09-18) Snider, Paige L.; Simmons, Olga; Conway, Simon J.; Pediatrics, School of Medicine
    Testicular development starts in utero and maturation continues postnatally, requiring a cascade of gene activation and differentiation into different cell types, with each cell type having its own specific function. As we had previously reported that the Capping protein inhibiting regulator of actin (Cracd) gene was expressed in the adult mouse testis, herein we examine when and where the β-catenin associated Cracd is initially expressed during postnatal testis development. Significantly, Cracd mRNA is present in both the immature postnatal and adult testis in round spermatid cells, with highest level of expression occurring during the first wave of meiosis and spermatogenesis. In the juvenile testes, Cracd is initially expressed within the innermost region but as maturation occurs, Cracd mRNA switches to a more peripheral location. Thereafter, Cracd is downregulated to maintenance levels in the haploid male germ cell lineage. As Cracd mRNA was expressed within developing round spermatids, we tested its effectiveness as a biomarker of non-obstructive azoospermia using transgenic knockout mice models. Meaningfully, Cracd expression was absent in Deleted in azoospermia like (Dazl) null testis, which exhibit a dramatic germ cell loss. Moreover, Cracd was abnormally regulated and ectopically mis-expressed in Polypyrimidine tract binding protein-2 (Ptbp2) conditional germ cell restricted knockout testis, which exhibit a block during spermatid differentiation and a reduction in the number of late stage spermatocytes coincident with reduced β-catenin expression. Combined, these data suggest that Cracd is a useful first wave of spermatogenesis biomarker of azoospermia phenotypes, even prior to an overt phenotype being evident.
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    Human keratinocyte differentiation requires translational control by the eIF2α kinase GCN2
    (Elsevier, 2017) Collier, Ann E.; Wek, Ronald C.; Spandau, Dan F.; Department of Dermatology, IU School of Medicine
    Appropriate and sequential differentiation of keratinocytes is essential for all functions of the human epidermis. While transcriptional regulation has proven to be important for keratinocyte differentiation, little is known about the role of translational control. A key mechanism for modulating translation is through phosphorylation of the α subunit of eIF2. A family of different eIF2α kinases function in the integrative stress response to inhibit general protein synthesis coincident with preferential translation of select mRNAs that participate in stress alleviation. Here we demonstrate that translational control through eIF2α phosphorylation is required for normal keratinocyte differentiation. Analyses of polysome profiles revealed that key differentiation genes, including involucrin, are bound to heavy polysomes during differentiation, despite decreased general protein synthesis. Induced eIF2α phosphorylation by the GCN2 protein kinase facilitated translational control and differentiation-specific protein expression during keratinocyte differentiation. Furthermore, loss of GCN2 thwarted translational control, normal epidermal differentiation, and differentiation gene expression in organotypic skin culture. These findings underscore a previously unknown function for GCN2 phosphorylation of eIF2α and translational control in the formation of an intact human epidermis.
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    Human Neural Stem Cells in Space Proliferate more than Ground Control Cells: Implications for Long-Term Space Travel
    (Herald, 2021-04) Shaka, Sophia; Carpo, Nicholas; Tran, Victoria; Ma, Yao-Ying; Karouia, Fathi; Espinosa-Jeffrey, Araceli; Pharmacology and Toxicology, School of Medicine
    Long-term travel and lengthy stays for astronauts in outer space are imminent. To date, more than 500 astronauts have experienced the extreme conditions of space flight including microgravity and radiation. For the past decade, many studies associated with long-duration spaceflight have shown the recurring occurrence of ophthalmic abnormalities. The reasons of the observed changes in some astronauts remained unclear. However, factors such as the increase in intracranial pressure and fluid shifts are among the top potential contributing elements. Here we report a study that specifically looked at the effect of space environment on the proliferation and physiology of human Neural Stem Cells (NSCs) onboard the International Space Station (ISS) as compared to ground controls. The study revealed that human NSCs proliferated seven times more while in space (SPC) when compared to on Earth (1G) control cultures. We also examined by continuous live imaging the behavior of space flown NSCs upon return to Earth. We found that after space flight, they continued proliferating at the same pace as 1G controls. Interestingly, NSCs flown to space displayed a larger diameter than control cells. These phenomena, increased proliferation while in space and larger cell soma may contribute to intracranial hypertension found in astronauts, representing a risk factor and potential limitation to long duration space missions such as travelling to the Moon or Mars. In addition, NSCs are essential to maintain Central Nervous System (CNS) function, as they are the basis for the regeneration of CNS cell populations in health and disease.
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    The impact of hydroxyapatite on alkaline phosphatase activity and mineral deposition of dental pulp stem cells using a double antibiotic paste loaded methylcellulose carrier
    (2020) Fischer, Benjamin I.; Bruzzaniti, Angela; Spolnik, Kenneth; Ehrlich, Ygal; Bringas, Josef; Gregory, Richard
    Introduction: Regenerative endodontic procedures (REPs) are a type of endodontic treatment aimed at replacing damaged tooth structures, including dentin and root structures, as well as cells of the pulp-dentin complex. Double antibiotic paste (DAP) has been shown to be efficacious in achieving disinfection of the root canal system while minimizing cytotoxicity to dental pulp stem cells (DPSCs). Hydroxyapatite (HA) is an extracellular, mineralized component of bone that has shown much promise as a scaffold in the field of regenerative medicine. Objective: The objective of this study was to evaluate the effects of HA in a DAP loaded methylcellulose (MC) carrier on the differentiation and mineral deposition of DPSC over time. Materials and Methods: DPSCs were plated in 24-well plates with culture media. The following day, semi-permeable 0.1 m chambers were inserted into the wells to separate the reservoirs and permit delivery of medicaments. 100 L treatment paste composed of MC with 1% DAP and either 0.5% or 1.0% nano-HA was added, followed by additional culture media. After 3 days of treatment, medicaments were removed and DPSCs were cultured for an additional 9 days with replacement of media every 3-4 days. At Day 12, DPSCs were evaluated for alkaline phosphatase (ALP) activity using a biochemical assay and mineral deposition using an Alizarin Red S Ca2+ staining assay (4 wells/group). Comparisons between groups were performed using one-way analysis of variance (ANOVA) with a 5% significance level used for all tests. Results: A trend towards increased ALP and mineral deposition activity was noted among the groups with HA added to DAP with MC. Although these trends were not statistically significant, a trend towards increased ALP and mineral deposition was observed after 3-day medicament exposure. The results were similar to previous findings using 7-day medicament treatments. Conclusion: The addition of HA showed a trend towards improved differentiation and mineral deposition of DPSCs compared to DAP with MC. Although additional studies are required, these results showed suggest that even with a shortened treatment time, increased differentiation and mineral deposition of DPSCs may be possible. This study provides additional support that low concentration DAP in a MC carrier has potential application in regenerative endodontic procedures. The novel addition of HA may provide additional osteogenic potential.
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    Organizational sensegiving: Indicators and nonprofit signaling
    (Wiley, 2019) Levine Daniel, Jamie; Eckerd, Adam; School of Public and Environmental Affairs
    Resource acquisition depends upon the agreement between an organization's sense of identity and the perceptions of organizational identity held by resource providers. To smooth the flow of resources and buffer against potential issues, organizations seek to manage external perceptions and, to the extent possible, control their organizational identity. Using exploratory factor analysis, we examine the data from 300 GuideStar profiles to develop a sense of how nonprofit organizations “give sense” to resource providers and attempt to manage their organizational identity. We find evidence of three sensegiving strategies. We then use a seemingly unrelated regression model to examine the relationship between these strategies and revenue outcomes, finding evidence that (a) nonprofit organizations demonstrate intentional sensegiving, and (b) different sensegiving approaches are related to different income streams.
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    Potential for Stem Cells Therapy in Alzheimer’s Disease: Do Neurotrophic Factors Play Critical Role?
    (Bentham, 2017) Bali, Parul; Lahiri, Debomoy K.; Banik, Avijit; Nehru, Bimla; Anand, Akshay; Department of Psychiatry, IU School of Medicine
    Alzheimer’s disease (AD) is one of the most common causes of dementia. Despite several decades of research in AD, there is no standard disease- modifying therapy available and currentlyapproved drugs provide only symptomatic relief. Stem cells hold immense potential to regenerate damaged tissues and are currently tested in some brain-related disorders, such as AD, amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). We review stem cell transplantation studies using preclinical and clinical tools. We describe different sources of stem cells used in various animal models and explaining the putative molecular mechanisms that can rescue neurodegenerative disorders. The clinical studies suggest safety, efficacy and translational potential of stem cell therapy. The therapeutic outcome of stem cell transplantation has been promising in many studies, but no unifying hypothesis can convincingly explain the underlying mechanism. Some studies have reported paracrine effects exerted by these stem cells via the release of neurotrophic factors, while other studies describe the immunomodulatory effects exerted by the transplanted cells. There are also reports which indicate that stem cell transplantation might result in endogenous cell proliferation or replacement of diseased cells. In animal models of AD, stem cell transplantation is also believed to increase expression of synaptic proteins.
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    Retinal Ganglion Cells With a Glaucoma OPTN(E50K) Mutation Exhibit Neurodegenerative Phenotypes when Derived from Three-Dimensional Retinal Organoids
    (Elsevier, 2020-07-14) VanderWall, Kirstin B.; Huang, Kang-Chieh; Pan, Yanling; Lavekar, Sailee S.; Fligor, Clarisse M.; Allsop, Anna R.; Lentsch, Kelly A.; Dang, Pengtao; Zhang, Chi; Tseng, Henry C.; Cummins, Theodore R.; Meyer, Jason S.; Medical and Molecular Genetics, School of Medicine
    Retinal ganglion cells (RGCs) serve as the connection between the eye and the brain, with this connection disrupted in glaucoma. Numerous cellular mechanisms have been associated with glaucomatous neurodegeneration, and useful cellular models of glaucoma allow for the precise analysis of degenerative phenotypes. Human pluripotent stem cells (hPSCs) serve as powerful tools for studying human disease, particularly cellular mechanisms underlying neurodegeneration. Thus, efforts focused upon hPSCs with an E50K mutation in the Optineurin (OPTN) gene, a leading cause of inherited forms of glaucoma. CRISPR/Cas9 gene editing introduced the OPTN(E50K) mutation into existing lines of hPSCs, as well as generating isogenic controls from patient-derived lines. RGCs differentiated from OPTN(E50K) hPSCs exhibited numerous neurodegenerative deficits, including neurite retraction, autophagy dysfunction, apoptosis, and increased excitability. These results demonstrate the utility of OPTN(E50K) RGCs as an in vitro model of neurodegeneration, with the opportunity to develop novel therapeutic approaches for glaucoma.