ASU Scholarship Showcase

Neural progenitor cells (NPCs) derived from human pluripotent stem cells (hPSCs) are a multipotent cell population that is capable of nearly indefinite expansion and subsequent differentiation into the various neuronal and supporting cell types that comprise the CNS. However, current protocols for differentiating NPCs toward neuronal lineages result in a mixture of neurons from various regions of the CNS. In this study, we determined that endogenous WNT signaling is a primary contributor to the heterogeneity observed in NPC cultures and neuronal differentiation. Furthermore, exogenous manipulation of WNT signaling during neural differentiation, through either activation or inhibition, reduces this heterogeneity in NPC cultures, thereby promoting the formation of regionally homogeneous NPC and neuronal cultures. The ability to manipulate WNT signaling to generate regionally specific NPCs and neurons will be useful for studying human neural development and will greatly enhance the translational potential of hPSCs for neural-related therapies.

Objective: This cross sectional study aims to determine the effects of gender and parental perception of safety at school on children’s physical activity (PA) levels.

Materials and Methods: Parents of school aged Mexican children residing in Guadalajara, Mexico City, and Puerto Vallarta, completed surveys about their children’s PA measures. The physical activity indicators were evaluated using linear and logistical regression models.

Results: Analysis did not indicate that gender moderated the relationship between parental perception of safety and PA measures, but significant gender issues exist with girls participating less than boys in the three measures of PA in this study (p<0.001).

Conclusion: Results suggest the need for additional interventions promoting physical activity in girls in Mexico.

Gas seeps emanating from Yanartaş (Chimera), Turkey, have been documented for thousands of years. Active serpentinization produces hydrogen and a range of carbon gases that may provide fuel for life. Here we report a newly discovered, ephemeral fluid seep emanating from a small gas vent at Yanartaş. Fluids and biofilms were sampled at the source and points downstream. We describe site conditions, and provide microbiological data in the form of enrichment cultures, Scanning electron microscopy (SEM), carbon and nitrogen isotopic composition of solids, and PCR screens of nitrogen cycle genes. Source fluids are pH 11.95, with a Ca:Mg of ~200, and sediments under the ignited gas seep measure 60°C. Collectively, these data suggest the fluid is the product of active serpentinization at depth. Source sediments are primarily calcite and alteration products (chlorite and montmorillonite). Downstream, biofilms are mixed with montmorillonite. SEM shows biofilms distributed homogeneously with carbonates. Organic carbon accounts for 60% of the total carbon at the source, decreasing downstream to <15% as inorganic carbon precipitates. δ¹³C ratios of the organic carbon fraction of solids are depleted (−25 to −28‰) relative to the carbonates (−11 to −20‰). We conclude that heterotrophic processes are dominant throughout the surface ecosystem, and carbon fixation may be key down channel. δ¹⁵N ratios ~3‰, and absence of nifH in extracted DNA suggest that nitrogen fixation is not occurring in sediments. However, the presence of narG and nirS at most locations and in enrichments indicates genomic potential for nitrate and nitrite reduction. This small seep with shallow run-off is likely ephemeral, but abundant preserved microterracettes in the outflow and the surrounding area suggest it has been present for some time. This site and others like it present an opportunity for investigations of preserved deep biosphere signatures, and subsurface-surface interactions.

Although the majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi003-A] and a non-demented control (NDC) patient [ASUi004-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and retained the ability to differentiate into cells representative of the three germ layers.

Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages.

Adult and pluripotent stem cells represent a ready supply of cellular raw materials that can be used to generate the functionally mature cells needed to replace damaged or diseased heart tissue. However, the use of stem cells for cardiac regenerative therapies is limited by the low efficiency by which stem cells are differentiated in vitro to cardiac lineages as well as the inability to effectively deliver stem cells and their derivatives to regions of damaged myocardium. In this review, we discuss the various biomaterial-based approaches that are being implemented to direct stem cell fate both in vitro and in vivo. First, we discuss the stem cell types available for cardiac repair and the engineering of naturally and synthetically derived biomaterials to direct their in vitro differentiation to the cell types that comprise heart tissue. Next, we describe biomaterial-based approaches that are being implemented to enhance the in vivo integration and differentiation of stem cells delivered to areas of cardiac damage. Finally, we present emerging trends of using stem cell-based biomaterial approaches to deliver pro-survival factors and fully vascularized tissue to the damaged and diseased cardiac tissue.

The field of tissue engineering entered a new era with the development of human pluripotent stem cells (hPSCs), which are capable of unlimited expansion whilst retaining the potential to differentiate into all mature cell populations. However, these cells harbor significant risks, including tumor formation upon transplantation. One way to mitigate this risk is to develop expandable progenitor cell populations with restricted differentiation potential. Here, we used a cellular microarray technology to identify a defined and optimized culture condition that supports the derivation and propagation of a cell population with mesodermal properties. This cell population, referred to as intermediate mesodermal progenitor (IMP) cells, is capable of unlimited expansion, lacks tumor formation potential, and, upon appropriate stimulation, readily acquires properties of a sub-population of kidney cells. Interestingly, IMP cells fail to differentiate into other mesodermally-derived tissues, including blood and heart, suggesting that these cells are restricted to an intermediate mesodermal fate.

Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages.

Over 100 hot spring sediment samples were collected from 28 sites in 12 areas/regions, while recording as many coincident geochemical properties as feasible (>60 analytes). PCR was used to screen samples for Korarchaeota 16S rRNA genes. Over 500 Korarchaeota 16S rRNA genes were screened by RFLP analysis and 90 were sequenced, resulting in identification of novel Korarchaeota phylotypes and exclusive geographical variants. Korarchaeota diversity was low, as in other terrestrial geothermal systems, suggesting a marine origin for Korarchaeota with subsequent niche-invasion into terrestrial systems. Korarchaeota endemism is consistent with endemism of other terrestrial thermophiles and supports the existence of dispersal barriers. Korarchaeota were found predominantly in >55°C springs at pH 4.7–8.5 at concentrations up to 6.6×10⁶ 16S rRNA gene copies g^-1 wet sediment. In Yellowstone National Park (YNP), Korarchaeota were most abundant in springs with a pH range of 5.7 to 7.0. High sulfate concentrations suggest these fluids are influenced by contributions from hydrothermal vapors that may be neutralized to some extent by mixing with water from deep geothermal sources or meteoric water. In the Great Basin (GB), Korarchaeota were most abundant at spring sources of pH<7.2 with high particulate C content and high alkalinity, which are likely to be buffered by the carbonic acid system. It is therefore likely that at least two different geological mechanisms in YNP and GB springs create the neutral to mildly acidic pH that is optimal for Korarchaeota. A classification support vector machine (C-SVM) trained on single analytes, two analyte combinations, or vectors from non-metric multidimensional scaling models was able to predict springs as Korarchaeota-optimal or sub-optimal habitats with accuracies up to 95%. To our knowledge, this is the most extensive analysis of the geochemical habitat of any high-level microbial taxon and the first application of a C-SVM to microbial ecology.

Many studies link the compositions of microbial communities to their environments, but the energetics of organism-specific biomass synthesis as a function of geochemical variables have rarely been assessed. We describe a thermodynamic model that integrates geochemical and metagenomic data for biofilms sampled at five sites along a thermal and chemical gradient in the outflow channel of the hot spring known as “Bison Pool” in Yellowstone National Park. The relative abundances of major phyla in individual communities sampled along the outflow channel are modeled by computing metastable equilibrium among model proteins with amino acid compositions derived from metagenomic sequences. Geochemical conditions are represented by temperature and activities of basis species, including pH and oxidation-reduction potential quantified as the activity of dissolved hydrogen. By adjusting the activity of hydrogen, the model can be tuned to closely approximate the relative abundances of the phyla observed in the community profiles generated from BLAST assignments. The findings reveal an inverse relationship between the energy demand to form the proteins at equal thermodynamic activities and the abundance of phyla in the community. The distance from metastable equilibrium of the communities, assessed using an equation derived from energetic considerations that is also consistent with the information-theoretic entropy change, decreases along the outflow channel. Specific divergences from metastable equilibrium, such as an underprediction of the relative abundances of phototrophic organisms at lower temperatures, can be explained by considering additional sources of energy and/or differences in growth efficiency. Although the metabolisms used by many members of these communities are driven by chemical disequilibria, the results support the possibility that higher-level patterns of chemotrophic microbial ecosystems are shaped by metastable equilibrium states that depend on both the composition of biomass and the environmental conditions.