Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA954860 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Research continues to identify genetic variation, environmental exposures, and their mixtures underlying different diseases and conditions. There is a need for screening methods to understand the molecular outcomes of such factors. Here, we investigate a highly efficient and multiplexable, fractional factorial experimental design (FFED) to study six environmental factors and four human induced pluripotent stem cell line derived differentiating human neural progenitors. We showcase the FFED coupled with RNA-sequencing to identify the effects of low-grade exposures to these environmental factors and analyse the results in the context of autism spectrum disorder (ASD). We performed this after five-day exposures on differentiating human neural progenitors accompanied by a layered analytical approach and detected several convergent and divergent, gene and pathway level responses. We revealed significant upregulation of pathways related to synaptic function and lipid metabolism following lead and fluoxetine exposure, respectively. The lipid changes were validated using mass spectrometry- based metabolomics after fluoxetine exposure. Our study demonstrates that the FFED can be used for multiplexed transcriptomic analyses to detect relevant pathway-level changes in human neural development caused by low-grade environmental risk factors. Future studies will require multiple cell lines with different genetic backgrounds for characterising the effects of environmental exposures in ASD.
2023-06-09 | GSE229546 | GEO
Project description:Research continues to identify genetic variation, environmental exposures, and their mixtures underlying different diseases and conditions. There is a need for screening methods to understand the molecular outcomes of such factors. Here, we investigate a highly efficient and multiplexable, fractional factorial experimental design (FFED) to study six environmental factors (lead, valproic acid, bisphenol A, ethanol, fluoxetine hydrochloride and zinc deficiency) and four human induced pluripotent stem cell line derived differentiating human neural progenitors. We showcase the FFED coupled with RNA-sequencing to identify the effects of low-grade exposures to these environmental factors and analyse the results in the context of autism spectrum disorder (ASD). We performed this after 5-day exposures on differentiating human neural progenitors accompanied by a layered analytical approach and detected several convergent and divergent, gene and pathway level responses. We revealed significant upregulation of pathways related to synaptic function and lipid metabolism following lead and fluoxetine exposure, respectively. Moreover, fluoxetine exposure elevated several fatty acids when validated using mass spectrometry-based metabolomics. Our study demonstrates that the FFED can be used for multiplexed transcriptomic analyses to detect relevant pathway-level changes in human neural development caused by low-grade environmental risk factors. Future studies will require multiple cell lines with different genetic backgrounds for characterising the effects of environmental exposures in ASD.
| S-EPMC10310850 | biostudies-literature
Project description:BackgroundPretreatments are one of the main bottlenecks for the lignocellulose conversion process and the search for cheaper and effective pretreatment methodologies for each biomass is a complex but fundamental task. Here, we used a 2ν5-1 fractional factorial design (FFD) to optimize five pretreatment variables: milling time, temperature, double treatment, chemical concentration, and pretreatment time in acid-alkali (EA) and acid-organosolv (EO) pretreatments, applied to elephant grass leaves.ResultsFFD allowed optimization of the pretreatment conditions using a reduced number of experiments and allowed the identification of secondary interactions between the factors. FFD showed that the temperature can be kept at its lower level and that the first acid step can be eliminated in both pretreatments, without significant losses to enzymatic hydrolysis. EA resulted in the highest release of reducing sugars (maximum of 205 mg/g substrate in comparison to 152 mg/g in EO and 40 mg/g in the untreated sample), using the following conditions in the alkali step: [NaOH] = 4.5% w/v; 85 °C and 100 min after ball milling the sample. The factors statistically significant (P < 0.05) in EA pretreatment were NaOH concentration, which contributes to improved hydrolysis by lignin and silica removal, and the milling time, which has a mechanical effect. For EO samples, the statistically significant factors to improved hydrolysis were ethanol and catalyst concentrations, which are both correlated to higher cellulose amounts in the pretreated substrates. The catalyst is also correlated to lignin removal. The detailed characterization of the main hemicellulosic sugars in the solids after pretreatments revealed their distinct recalcitrance: glucose was typically more recalcitrant than xylose and arabinose, which could be almost completely removed under specific pretreatments. In EA samples, the removal of hemicellulose derivatives was very dependent on the acid step, especially arabinose removal.ConclusionThe results presented herewith contribute to the development of more efficient and viable pretreatments to produce cellulosic ethanol from grass biomasses, saving time, costs and energy. They also facilitate the design of enzymatic cocktails and a more appropriate use of the sugars contained in the pretreatment liquors, by establishing the key recalcitrant polymers in the solids resulting from each processing step.
| S-EPMC6058377 | biostudies-literature
Project description:Fractional CO2 laser, as a typical ablative laser, has been used to assist in the treatment of many skin diseases, such as photoaging, atrophic scar, hypertrophic scar, superficial pigmentation, vitiligo, and so on. However, the dynamic changes in skin function after fractional CO2 laser treatment are still unclear. This study explored the changes in local skin function and possible regulatory mechanisms after fractional CO2 laser treatment for 1, 3, 5 and 7 days through transcriptome high-throughput sequencing. The results showed that fractional CO2 laser tended to transform the “lesions” into “normal skin”, regulate the skin barrier, coordinate the rearrangement of collagen, enhance the local microvascular circulation, activate the immune system to secrete a large number of cytokines, and act as an auxiliary tool to assist drug transport. According to the basic principle of destruction before reconstruction, fractional CO2 laser plays a key role of balancer in skin reconstruction. In conclusion, the gene expression profiles of fractional CO2 laser-treated skin undergo dynamic changes over time. Skin barrier, collagen arrangement, drug metabolism, immune system and skin defense system all present obvious characteristics of timing change after fractional CO2 laser treatment.
2023-06-17 | GSE234691 | GEO
Project description:Understanding the regulatory networks which control specific macrophage phenotypes is essential in identifying novel targets to correct macrophage mediated clinical disorders, often accompanied by inflammatory events. Since mesenchymal stromal cells (MSCs) have been shown to play key roles in regulating immune functions predominantly via a large number of secreted products, we used a fractional factorial approach to streamline experimental evaluation of MSC mediated inflammatory macrophage regulation. Our macrophage reprogramming metrics, human bone marrow MSC attenuation of macrophage pro-inflammatory M1 TNFα secretion and simultaneous enhanced expression of the M2 macrophage marker, CD206, were used as analysis endpoints. Objective evaluation of a panel of MSC secreted mediators indicated that PGE2 alone was sufficient in facilitating macrophage reprogramming, while IL4 only provided partial reprogramming. Inhibiting stromal cell PGE2 secretion with Indomethacin, reversed the macrophage reprogramming effect. PGE2 reprogramming was mediated through the EP4 receptor and indirectly through the CREB signaling pathway as GSK3 specific inhibitors induced M1 macrophages to express CD206. This reprogramming pathway functioned independently from the M1 suppression pathway, as neither CREB nor GSK3 inhibition reversed PGE2 TNF-α secretion attenuation. In conclusion, fractional factorial experimental design identified stromal derived PGE2 as the factor most important in facilitating macrophage reprogramming, albeit via two unique pathways.
| S-EPMC5928506 | biostudies-literature
Project description:Ablative fractional laser treatment is considered the gold standard for skin rejuvenation. In order to understand how fractional laser works to rejuvenate skin, we performed microarray profiling on skin biopsies to identify temporal and dose-response changes in gene expression following fractional laser treatment.
2021-11-07 | GSE168760 | GEO
Project description:Retinal cells are specified in a zebrafish recessive mutant called young (yng) but they fail to terminally differentiate; i.e. extend neurites and make synaptic contacts. A point mutation in a brahma-related gene 1 (brg1) is responsible for this phenotype. In this microarray study, a three-factor factorial design was utilized to investigate the effects of 1) mutation, 2) change in time (36 vs. 52hpf), and 3) change in tissue (retina vs. whole embryos), and their interactions on gene expression. Significant probesets were inferred by using both specific contrasts of the fitted Analysis of Variance (ANOVA) models and a corresponding 2-fold expression cutoff. The probesets were grouped into three broad categories: 1) Brg1-regulated retinal differentiation genes (731 probsets), 2) Retinal specific genes but independent of Brg1 regulation (3038 probesets) and 3) Genes regulated by Brg1 but outside the retina (107 probesets). Four gene groups/pathways including neurite outgrowth regulators, Delta-Notch signalling molecules, Irx family members and specific cell cycle regulators were identified in the first group, and their relevance for retinal differentiation functionally validated. This study demonstrates that an approach such as ours can identify relevant genes and pathways involved in retinal development as well as the development of other tissues at the same time. Keywords: Development, retina, terminal differentiation, chromatin remodeling, factorial anlaysis
2008-08-04 | GSE8874 | GEO
Project description:We applied a custom 2k micro-array with 2232 oligonucleotide sequences (50-70 nt) to a factorial with 13 parental inbred lines (9 Dent, 4 Flint) of European maize (Zea mays L.). The selection of oligonucleotides was based on 47k-array expression data from a 14x7 factorial with 98 hybrids (GSE17754). The main fraction of oligonucleotides (1639) represents genes that showed differential expression between the parental genotypes in the 14x7 factorial and consistent association with HP for GY in cross validation runs to estimate prediction accuracies for this trait. In addition the array contains partial overlapping fractions of genes that correlated with HP/GY (378), HP/GDMC (200), or MPH/GY (345) and 205 representatives of the 6 most overrepresented biological processes among genes correlated with HP/GY in the 14x7 factorial.
2016-08-18 | GSE85288 | GEO
Project description:We applied a custom 2k micro-array with 2232 oligonucleotide sequences (50-70 nt) to a factorial with 13 parental inbred lines (9 Dent, 4 Flint) of European maize (Zea mays L.). The selection of oligonucleotides was based on 47k-array expression data from a 14x7 factorial with 98 hybrids (GSE17754). The main fraction of oligonucleotides (1639) represents genes that showed differential expression between the parental genotypes in the 14x7 factorial and consistent association with HP for GY in cross validation runs to estimate prediction accuracies for this trait. In addition the array contains partial overlapping fractions of genes that correlated with HP/GY (378), HP/GDMC (200), or MPH/GY (345) and 205 representatives of the 6 most overrepresented biological processes among genes correlated with HP/GY in the 14x7 factorial.
2016-08-18 | GSE85286 | GEO
Project description:We applied a custom 2k micro-array with 2232 oligonucleotide sequences (50-70 nt) to a factorial with 29 parental inbred lines (16 Dent,13 Flint) of European maize (Zea mays L.). The selection of oligonucleotides was based on 47k-array expression data from a 14x7 factorial with 98 hybrids (GSE17754). The main fraction of oligonucleotides (1639) represents genes that showed differential expression between the parental genotypes in the 14x7 factorial and consistent association with HP for GY in cross validation runs to estimate prediction accuracies for this trait. In addition the array contains partial overlapping fractions of genes that correlated with HP/GY (378), HP/GDMC (200), or MPH/GY (345) and 205 representatives of the 6 most overrepresented biological processes among genes correlated with HP/GY in the 14x7 factorial.
2016-08-18 | GSE85285 | GEO