scholarly journals Dynamic Characterization of Structural, Molecular, and Electrophysiological Phenotypes of Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids, and Comparison with Fetal and Adult Gene Profiles

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1301 ◽  
Author(s):  
Sarah Logan ◽  
Thiago Arzua ◽  
Yasheng Yan ◽  
Congshan Jiang ◽  
Xiaojie Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Adult Brain ◽  
Brain Diseases ◽  
Gene Profiles ◽  
Health And Disease ◽  
Induced Pluripotent ◽  
First Time

Background: The development of 3D cerebral organoid technology using human-induced pluripotent stem cells (iPSCs) provides a promising platform to study how brain diseases are appropriately modeled and treated. So far, understanding of the characteristics of organoids is still in its infancy. The current study profiled, for the first time, the electrophysiological properties of organoids at molecular and cellular levels and dissected the potential age equivalency of 2-month-old organoids to human ones by a comparison of gene expression profiles among cerebral organoids, human fetal and adult brains. Results: Cerebral organoids exhibit heterogeneous gene and protein markers of various brain cells, such as neurons, astrocytes, and vascular cells (endothelial cells and smooth muscle cells) at 2 months, and increases in neural, glial, vascular, and channel-related gene expression over a 2-month differentiation course. Two-month organoids exhibited action potentials, multiple channel activities, and functional electrophysiological responses to the anesthetic agent propofol. A bioinformatics analysis of 20,723 gene expression profiles showed the similar distance of gene profiles in cerebral organoids to fetal and adult brain tissues. The subsequent Ingenuity Pathway Analysis (IPA) of select canonical pathways related to neural development, network formation, and electrophysiological signaling, revealed that only calcium signaling, cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signaling in neurons, glutamate receptor signaling, and synaptogenesis signaling were predicted to be downregulated in cerebral organoids relative to fetal samples. Nearly all cerebral organoid and fetal pathway phenotypes were predicted to be downregulated compared with adult tissue. Conclusions: This novel study highlights dynamic development, cellular heterogeneity and electrophysiological activity. In particular, for the first time, electrophysiological drug response recapitulates what occurs in vivo, and neural characteristics are predicted to be highly similar to the human brain, further supporting the promising application of the cerebral organoid system for the modeling of the human brain in health and disease. Additionally, the studies from these characterizations of cerebral organoids in multiple levels and the findings from gene comparisons between cerebral organoids and humans (fetuses and adults) help us better understand this cerebral organoid-based cutting-edge platform and its wide uses in modeling human brain in terms of health and disease, development, and testing drug efficacy and toxicity.

scholarly journals Time Dependent Gene Expression Changes in the Liver of Mice Treated with Benzene

2008 ◽  
Vol 3 ◽  
pp. BMI.S590 ◽  
Author(s):  
Han-Jin Park ◽  
Jung Hwa Oh ◽  
Seokjoo Yoon ◽  
S.V.S. Rana
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
General Purpose ◽  
Time Dependent ◽  
Expression Data ◽  
Benzene Exposure ◽  
Microarray Analyses ◽  
First Time ◽  
Affymetrix Gene Chip

Benzene is used as a general purpose solvent. Benzene metabolism starts from phenol and ends with p-benzoquinone and o-benzoquinone. Liver injury inducted by benzene still remains a toxicologic problem. Tumor related genes and immune responsive genes have been studied in patients suffering from benzene exposure. However, gene expression profiles and pathways related to its hepatotoxicity are not known. This study reports the results obtained in the liver of BALB/C mice (SLC, Inc., Japan) administered 0.05 ml/100 g body weight of 2% benzene for six days. Serum, ALT, AST and ALP were determined using automated analyzer (Fuji., Japan). Histopathological observations were made to support gene expression data. c-DNA microarray analyses were performed using Affymetrix Gene-chip system. After six days of benzene exposure, twenty five genes were down regulated whereas nineteen genes were up-regulated. These gene expression changes were found to be related to pathways of biotransformation, detoxification, apoptosis, oxidative stress and cell cycle. It has been shown for the first time that genes corresponding to circadian rhythms are affected by benzene. Results suggest that gene expression profile might serve as potential biomarkers of hepatotoxicity during benzene exposure.

scholarly journals Analysis of blood-based gene expression in idiopathic Parkinson disease

Neurology ◽  
2017 ◽  
Vol 89 (16) ◽  
pp. 1676-1683 ◽  
Author(s):  
Ron Shamir ◽  
Christine Klein ◽  
David Amar ◽  
Eva-Juliane Vollstedt ◽  
Michael Bonin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson Disease ◽  
Gene Networks ◽  
Large Scale ◽  
Expression Profiles ◽  
Area Under The Curve ◽  
Gene Expression Profiles ◽  
Gene Signature ◽  
Gene Profiles ◽  
Independent Test

Objective:To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples).Methods:Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks.Results:A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E–6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E–4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1, ATP5A1, and VDAC3.Conclusions:We present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers.

scholarly journals Comparative Transcriptome Analysis of Different Dendrobium Species Reveals Active Ingredients-Related Genes and Pathways

2020 ◽  
Vol 21 (3) ◽  
pp. 861 ◽  
Author(s):  
Yingdan Yuan ◽  
Bo Zhang ◽  
Xinggang Tang ◽  
Jinchi Zhang ◽  
Jie Lin
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Rna Seq ◽  
Active Ingredients ◽  
Hub Genes ◽  
Transcriptome Database ◽  
Gene Modules ◽  
Functional Investigation ◽  
First Time

Dendrobium is widely used in traditional Chinese medicine, which contains many kinds of active ingredients. In recent years, many Dendrobium transcriptomes have been sequenced. Hence, weighted gene co-expression network analysis (WGCNA) was used with the gene expression profiles of active ingredients to identify the modules and genes that may associate with particular species and tissues. Three kinds of Dendrobium species and three tissues were sampled for RNA-seq to generate a high-quality, full-length transcriptome database. Based on significant changes in gene expression, we constructed co-expression networks and revealed 19 gene modules. Among them, four modules with properties correlating to active ingredients regulation and biosynthesis, and several hub genes were selected for further functional investigation. This is the first time the WGCNA method has been used to analyze Dendrobium transcriptome data. Further excavation of the gene module information will help us to further study the role and significance of key genes, key signaling pathways, and regulatory mechanisms between genes on the occurrence and development of medicinal components of Dendrobium.

scholarly journals Integrated analysis of the aging brain transcriptome and proteome in tauopathy

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Carl Grant Mangleburg ◽  
Timothy Wu ◽  
Hari K. Yalamanchili ◽  
Caiwei Guo ◽  
Yi-Chen Hsieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Mutant Form ◽  
Brain Gene Expression ◽  
Brain Transcriptome ◽  
Age Dependent

Abstract Background Tau neurofibrillary tangle pathology characterizes Alzheimer’s disease and other neurodegenerative tauopathies. Brain gene expression profiles can reveal mechanisms; however, few studies have systematically examined both the transcriptome and proteome or differentiated Tau- versus age-dependent changes. Methods Paired, longitudinal RNA-sequencing and mass-spectrometry were performed in a Drosophila model of tauopathy, based on pan-neuronal expression of human wildtype Tau (TauWT) or a mutant form causing frontotemporal dementia (TauR406W). Tau-induced, differentially expressed transcripts and proteins were examined cross-sectionally or using linear regression and adjusting for age. Hierarchical clustering was performed to highlight network perturbations, and we examined overlaps with human brain gene expression profiles in tauopathy. Results TauWT induced 1514 and 213 differentially expressed transcripts and proteins, respectively. TauR406W had a substantially greater impact, causing changes in 5494 transcripts and 697 proteins. There was a ~ 70% overlap between age- and Tau-induced changes and our analyses reveal pervasive bi-directional interactions. Strikingly, 42% of Tau-induced transcripts were discordant in the proteome, showing opposite direction of change. Tau-responsive gene expression networks strongly implicate innate immune activation. Cross-species analyses pinpoint human brain gene perturbations specifically triggered by Tau pathology and/or aging, and further differentiate between disease amplifying and protective changes. Conclusions Our results comprise a powerful, cross-species functional genomics resource for tauopathy, revealing Tau-mediated disruption of gene expression, including dynamic, age-dependent interactions between the brain transcriptome and proteome.

scholarly journals The origin, fate and function of macrophages in the peripheral nervous system—an update

2020 ◽  
Vol 32 (11) ◽  
pp. 709-717 ◽  
Author(s):  
Lukas Amann ◽  
Marco Prinz
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Rna Sequencing ◽  
Peripheral Nervous System ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
New Techniques ◽  
Macrophage Populations ◽  
And Function ◽  
First Time

Abstract The field of macrophage biology has made enormous progress over recent years. This was triggered by the advent of several new techniques such as the establishment of Cre/loxP-based transgenic mouse models that allowed for the first time delineation of the ontogeny and function of specific macrophage populations across many tissues. In addition, the introduction of new high-throughput technologies like bulk RNA sequencing and later single-cell RNA sequencing as well as advances in epigenetic analysis have helped to establish gene expression profiles, enhancer landscapes and local signaling cues that define and shape the identity of diverse macrophage populations. Nonetheless, some macrophage populations, like the ones residing in the peripheral nervous system (PNS), have not been studied in such detail yet. Here, we discuss recent studies that shed new light on the ontogeny, heterogeneity and gene expression profiles of resident macrophages in peripheral nerves and described differential activation of macrophage subsets during and after acute sciatic nerve injury.

scholarly journals Comparison of Stemness and Gene Expression between Gingiva and Dental Follicles in Children

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Chung-Min Kang ◽  
Seong-Oh Kim ◽  
Mijeong Jeon ◽  
Hyung-Jun Choi ◽  
Han-Sung Jung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Pcr Analysis ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Stem Cell Source ◽  
Regenerative Dentistry ◽  
Induced Pluripotent

The aim of this study was to compare the differential gene expression and stemness in the human gingiva and dental follicles (DFs) according to their biological characteristics. Gingiva (n=9) and DFs (n=9) were collected from 18 children. Comparative gene expression profiles were collected using cDNA microarray. The expression of development, chemotaxis, mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSs) related genes was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Histological analysis was performed using hematoxylin-eosin and immunohistochemical staining. Gingiva had greater expression of genes related to keratinization, ectodermal development, and chemotaxis whereas DFs exhibited higher expression levels of genes related to tooth and embryo development. qRT-PCR analysis showed that the expression levels of iPSc factors includingSOX2,KLF4, andC-MYCwere58.5±26.3,12.4±3.5, and12.2±1.9times higher in gingiva andVCAM1(CD146) andALCAM(CD166) were33.5±6.9and4.3±0.8times higher in DFs. Genes related to MSCs markers includingCD13,CD34,CD73,CD90, andCD105were expressed at higher levels in DFs. The results of qRT-PCR and IHC staining supported the microarray analysis results. Interestingly, this study demonstrated transcription factors of iPS cells were expressed at higher levels in the gingiva. Given the minimal surgical discomfort and simple accessibility, gingiva is a good candidate stem cell source in regenerative dentistry.

Analysis of Gene Expression in Patients with Acute Graft Versus Host Disease (GVHD) Following Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 729-729 ◽  
Author(s):  
Laura Tabellini ◽  
Ming-Tseh Lin ◽  
Wenhong Fan ◽  
Era Pogosova-Agadjanyan ◽  
Bart Stephens ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Blood Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Cellular Stress Response ◽  
Statistical Criterion ◽  
Gene Profiles ◽  
Clinically Significant

Abstract To better understand the cellular events that precede onset of clinically significant acute GVHD, a complication of allogeneic HSCT, we compared global gene expression profiles in patients 3 (days 18–22) and 4 (days 28–32) weeks after transplant. Patients in this study underwent myeloablative-conditioning regimen prior to receiving a T cell replete PBSCT from a related (n=9) or unrelated donor (5 HLA matched and 4 mismatched). Blood was obtained prospectively at scheduled times (prior to administration of glucocorticosteroids). RNA was isolated from nucleated blood cells and biotin-labeled cRNA hybridized on Affymetrix HG-U133A chips. MAS 5.0 software was used to extract gene expression values. We initially compared gene expression profiles between 15 patients 3 weeks post-HSCT and 10 normal controls. A total of 1176 genes were differentially expressed with statistical criterion of NFD (number of false discovery) equal to 10. Gene profiles for these 1176 genes were compared between 8 patients who subsequently developed GVHD within 1–5 days and 7 patients who remained GVHD free for 90 days. A limited number of genes were differentially expressed with NFD=1: 3 genes in GVHD patients showed increased expression and 6 showed decreased expression. A second set of experiments was performed to compare changes occurring within individual patients over an interval of 7 days (between weeks 3 and 4) prior to diagnosis of clinically significant GVHD (onset between days 27–32). We used a pair-wise comparison with selection criterion NFD=1. Increased expression prior to GVHD was observed in 55 genes and decreased expression in 88 genes. Approximately 50 of these genes were associated with inflammation and cellular stress response. Using the same statistical criterion we compared gene profiles between weeks 3 and 4 for 3 patients who remained GVHD-free for at least 90 days. Fewer changes were observed with increased expression occurring in 6 genes and decreased expression in 14 genes. These differentially expressed genes did not overlap with the candidate genes associated with the development of GVHD. Genes showing expression changes in GVHD included: Increased Decreased Inflamamtory Response IFN-α10, IL8, IL17 Transcription Factors NFATC1 GATA3 Cell Surface/Signal Transduction CD6, CD7, CD8, TCR-interacting molecule, MAP4K1, TNFRSF25, Effectors Molecules GRMM AICD/Apoptosis TOSO, BAX Cellular Stress Response DDAH1 DLAT, PKC1, COX5B These results suggest that extensive complex gene expression changes occur among nucleated blood cells during the early post-transplant period presumably due to extensive alterations in cellular activation occurring during reconstitution. The preliminary results of the longitudinal analysis of changes occurring within individual patients indicate that early post-transplant studies are feasible and that they may be informative for yielding insight into the molecular events associated with development of clinically significant GVHD. These data also indicate a paradoxical decrease in certain T cell associated genes in GVHD. However alloimmune induced T cell activation may lead to AICD and previous studies have demonstrated increased apoptosis among peripheral blood T cells in GVHD patients. Further studies including gene expression profiling of isolated T cells will be necessary to determine if this approach can be useful in identifying a molecular “signature” for GVHD that may be useful for diagnosis and monitoring.

scholarly journals Differences in the Gene Expression Profiles of Slow- and Fast-Forming Preinduced Pluripotent Stem Cell Colonies

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Sujin Kwon ◽  
Jung Sun Park ◽  
Byungkuk Min ◽  
Yong-Kook Kang
Keyword(s):  
Gene Expression ◽  
Mode Of Action ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Total Activity ◽  
Gradual Process ◽  
Stochastic Events ◽  
Induced Pluripotent ◽  
The Given ◽  
Pluripotency Genes

Induced pluripotent stem cells (iPSCs) are generated through a gradual process in which somatic cells undergo a number of stochastic events. In this study, we examined whether two different doxycycline-inducible iPSCs, slow-forming 4F2A-iPSCs and fast-forming NGFP-iPSCs, have equivalent levels of pluripotency. Multiplex reverse-transcriptase PCR generated gene expression profiles (GEPs) of 13 pluripotency genes in single initially formed-iPSC (if-iPSC) colonies of NGFP and 4F2A group. Assessment of GEP difference using a weighted root mean square deviation (wRMSD) indicates that 4F2A if-iPSCs are more closely related to mESCs than NGFP if-iPSCs. Consistently,NanogandSox2genes were more frequently derepressed in 4F2A if-iPSC group. We further examined 20 genes that are implicated in reprogramming. They were, overall, more highly expressed in NGFP if-iPSCs, differing from the pluripotency genes being more expressed in 4F2A if-iPSCs. wRMSD analysis for these reprogramming-related genes confirmed that the 4F2A if-iPSC colonies were less deviated from mESCs than the NGFP if-iPSC colonies. Our findings suggest that more important in attaining a better reprogramming is the mode of action by the given reprogramming factors, rather than the total activity of them exerting to the cells, as the thin-but-long-lasting mode of action in 4F2A if-iPSCs is shown to be more effective than its full-but-short-lasting mode in NGFP if-iPSCs.

scholarly journals Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance

Blood ◽  
2016 ◽  
Vol 127 (15) ◽  
pp. 1896-1906 ◽  
Author(s):  
Bruno Paiva ◽  
Luis A. Corchete ◽  
Maria-Belen Vidriales ◽  
Noemi Puig ◽  
Patricia Maiso ◽  
...  
Keyword(s):  
Gene Expression ◽  
Residual Disease ◽  
Clonal Selection ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genomic Analysis ◽  
Biological Features ◽  
Key Points ◽  
First Time ◽  
Minimal Residual

Key Points We report for the first time the biological features of MRD cells in MM and unravel that clonal selection is already present at the MRD stage. MRD cells show a singular phenotypic signature that may result from persisting clones with different genetic and gene expression profiles.

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