scholarly journals Persistence of rhombomeric organisation in the postsegmental hindbrain

Development ◽  
1996 ◽  
Vol 122 (7) ◽  
pp. 2143-2152 ◽  
Author(s):  
R.J. Wingate ◽  
A. Lumsden
Keyword(s):  
Gene Expression ◽  
Radial Glia ◽  
Ventricular Zone ◽  
In Situ Hybridisation ◽  
Proliferating Cells ◽  
Nuclear Organisation ◽  
Transverse Pattern ◽  
Marginal Zones ◽  
The Impact

Rhombomeres are morphological varicosities of the neural tube that are present between embryonic day (E) 1.5 and E5 and are characterised by compartment organisation, segmentally neuronal organisation and spatially restricted patterns of gene expression. After E5, the segmented origins of the hindbrain become indistinct, while the adult hindbrain has an longitudinal columnar nuclear organisation. In order to assess the impact of the early transverse pattern on later longitudinal organisation, we have used orthotopic quail grafts and in situ hybridisation to investigate the long-term fate of rhombomeres in the embryonic chick hindbrain. The uniformity of mixing between quail and chick cells was first verified using short-term aggregation cultures. The dispersal of the progeny of individual rhombomeres (r) was then assessed by the unilateral, isochronic and orthotopic transplantation of either r2, r3, r4, r5 or r6 from quail to chick at embryonic day E2. In addition, orthotopic, partial rhombomere grafts, encompassing an inter-rhombomere boundary and adjacent rhombomere bodies were used to assess cell mixing within rhombomeres. Operated embryos were incubated to either E7 or E10 when chimaeric brains were removed. Quail cells were identified in whole mounts or serial sections using the quail-specific antibody QCPN. Subsequently, radial glia morphology was assessed either by immunohistochemistry or DiI labelling. A series of fixed hindbrains between E6 and E9 were probed for transcripts of Hoxa-2 and Hoxb-1. Fate-mapping reveals that the progeny of individual rhombomeres form stripes of cells running dorsoventrally through the hindbrain. This pattern of dispersal precisely parallels the array of radial glia. Although the postmitotic progeny of adjacent rhombomeres spread to some extent into each others' territory in intermediate and marginal zones, there is little or no mixing between rhombomeres in the ventricular zone, which thus remains compartmentalised long after the rhombomeric morphology disappears. Segmental gene expression within this layer is also maintained after E5. A more detailed analysis of mixing between proliferating cells, using partial rhombomere grafts, reveals that both mixing and growth are non-uniform within the ventricular layer, suggesting, in particular, that longitudinal expansion within this layer is restricted. Together, these observations suggest that rhombomeres do not disappear at E5, as has previously been supposed, rather they persist in the ventricular zone to at least E9, ensuring a continuity in the presumed segmental cues that specify neuroepithelial cells in the hindbrain.

scholarly journals The Impact of Long‐Term Physical Activity on Age‐Related Changes in Protein and Gene Expression

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Ian R Lanza ◽  
Daniel K Short ◽  
Kevin R Short ◽  
Yan W Asmann ◽  
Sreekumar Raghavakaimal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Age Related ◽  
The Impact ◽  
Age Related Changes

Replicative Senescence-Associated Gene Expression Changes In Human MSPCs Independent of Genomic Variations

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4775-4775
Author(s):  
Katharina Schallmoser ◽  
Christina Bartmann ◽  
Eva Rohde ◽  
Simone Bork ◽  
Christian Guelly ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Bone Marrow ◽  
Large Scale ◽  
Replicative Senescence ◽  
Genomic Stability ◽  
The State ◽  
Efficient Treatment ◽  
The Impact

Abstract Abstract 4775 Background: Based on promising experimental studies with mesenchymal stem and progenitor cells (MSPCs) multiple clinical trials have been initiated. In previous studies we have observed genomic stability of MSPCs after efficient short-term expansion in a humanized GMP compliant system with pooled human platelet lysate (pHPL) replacing fetal bovine serum (FBS) as the cell culture supplement (Schallmoser K. and Strunk D., Journal of Visualized Experiments (32) DOI: 10.3791/1523, 2009). Notably, depending on culture protocols, an extensive propagation with highly variable cell culture duration may be necessary to yield enough MSPCs for therapy. The decline in proliferation rates of MSPCs in the course of the different long-term expansion procedures may indicate a propensity for replicative senescence which may hamper long term functionality in vivo. We have therefore initiated a molecular profiling of senescence-associated regulated genes to determine the state of senescence before MSPC transplantation. Methods: Human bone marrow-derived MSPCs were cultured following a highly efficient two-passage protocol (primary culture of unseparated bone marrow and subsequent large scale expansion; Schallmoser K. et al., Tissue Engineering 14:185-196, 2008) compared to conventional serial passaging in three different growth conditions with regularly more then four passages to obtain comparable final cell numbers. Culture media were either supplemented with FBS in different concentrations or pHPL. Gene expression changes were tested by microarray analysis and selected targets were reanalyzed by quantitative real-time PCR. The genomic stability of MSPCs after long-term culture was determined by array comparative genomic hybridization (CGH). Results: Despite high proliferation rate large scale expanded MSPCs showed genomic stability in array CGH. Long-term MSPC growth induced similar gene expression changes in MSPCs irrespective of isolation and expansion conditions. In particular, genes involved in cell differentiation, apoptosis and cell death were up-regulated, whereas genes involved in mitosis and proliferation were down-regulated. Furthermore, overlapping senescence-associated gene expression changes were found in all MSPC preparations. The genomic copy number variations detected in MSPCs of early and late passages in all culture conditions did not coincide with differentially expressed genes. Conclusion: Our data indicate that MSPC expansion can induce gene expression changes independent of isolation and FBS-supplemented as well as FBS-free expansion conditions. A panel of genes will be presented that might offer a practicable approach to assess MSPC quality with regard to the state of replicative senescence in advance of therapeutic application. Determining the impact of senescence acquired during cell expansion on the therapeutic potential of MSCPs for both immune modulation and organ regeneration may help to develop more efficient treatment strategies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Exploring the Impact of Cerebrovascular Disease and Major Depression on Non-diseased Human Tissue Transcriptomes

2021 ◽  
Vol 12 ◽  
Author(s):  
Chi-Lam Poon ◽  
Cho-Yi Chen
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Major Depression ◽  
Cerebrovascular Disease ◽  
Human Body ◽  
Association Studies ◽  
Complex Diseases ◽  
Functional Enrichment ◽  
The Impact

BackgroundThe development of complex diseases is contributed by the combination of multiple factors and complicated interactions between them. Inflammation has recently been associated with many complex diseases and may cause long-term damage to the human body. In this study, we examined whether two types of complex disease, cerebrovascular disease (CVD) or major depression (MD), systematically altered the transcriptomes of non-diseased human tissues and whether inflammation is linked to identifiable molecular signatures, using post-mortem samples from the Genotype-Tissue Expression (GTEx) project.ResultsFollowing a series of differential expression analyses, dozens to hundreds of differentially expressed genes (DEGs) were identified in multiple tissues between subjects with and without a history of CVD or MD. DEGs from these disease-associated tissues—the visceral adipose, tibial artery, caudate, and spinal cord for CVD; and the hypothalamus, putamen, and spinal cord for MD—were further analyzed for functional enrichment. Many pathways associated with immunological events were enriched in the upregulated DEGs of the CVD-associated tissues, as were the neurological and metabolic pathways in DEGs of the MD-associated tissues. Eight gene-tissue pairs were found to overlap with those prioritized by our transcriptome-wide association studies, indicating a potential genetic effect on gene expression for circulating cytokine phenotypes.ConclusionCerebrovascular disease and major depression cause detectable changes in the gene expression of non-diseased tissues, suggesting that a possible long-term impact of diseases, lifestyles and environmental factors may together contribute to the appearance of “transcriptomic scars” on the human body. Furthermore, inflammation is probably one of the systemic and long-lasting effects of cerebrovascular events.

scholarly journals Lipodystrophy-like features after total body irradiation among survivors of childhood acute leukemia

2019 ◽  
Vol 8 (4) ◽  
pp. 349-359 ◽  
Author(s):  
Sandrine Visentin ◽  
Gérard Michel ◽  
Claire Oudin ◽  
Béatrice Cousin ◽  
Bénédicte Gaborit ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Leukemia ◽  
Total Body Irradiation ◽  
Adipocyte Differentiation ◽  
Liver Fat ◽  
Functional Characteristics ◽  
Total Body ◽  
Childhood Acute Leukemia ◽  
The Impact

Background/objective The number of long-term survivors of childhood acute leukemia (AL) is substantially growing. These patients are at high risk for metabolic syndrome (MS), especially those who received total body irradiation (TBI). The consequences of children’s irradiation on adipose tissue (AT) development in adulthood are currently unknown. The objective of this study is to assess the impact of TBI on AT of childhood AL survivors. Design We compared the morphological and functional characteristics of AT among survivors of childhood AL who developed MS and received (n = 12) or not received (n = 12) TBI. Subjects/methods Body fat distribution and ectopic fat stores (abdominal visceral and liver fat) were evaluated by DEXA, MRI and 1H-spectroscopy. Functional characteristics of subcutaneous AT were investigated by studying gene expression and pre-adipocyte differentiation in culture. Results Patients who have received TBI exhibited a lower BMI (minus 5 kg/m2) and a lower waist circumference (minus 14 cm), especially irradiated women. Despite the lower quantity of intra-abdominal AT, irradiated patient displayed a nearly two-fold greater content of liver fat when compared to non-irradiated patient (17 vs 9%, P = 0.008). These lipodystrophic-like features are supplemented by molecular abnormalities in subcutaneous AT of irradiated patients: decrease of gene expression of SREBP1 (minus 39%, P = 0.01) and CIDEA (minus 36%, P = 0.004) and a clear alteration of pre-adipocyte differentiation. Conclusions These results strongly support the direct effect of irradiation on AT, especially in women, leading to specific nonalcoholic fatty liver disease, despite lower BMI. A long-term appropriate follow-up is necessary for these patients.

scholarly journals Long-Term Impact of Zinc Oxide Nanoparticles on Differentiation and Cytokine Secretion of Human Adipose-Derived Stromal Cells

Materials ◽  
2019 ◽  
Vol 12 (11) ◽  
pp. 1823 ◽  
Author(s):  
Katrin Radeloff ◽  
Andreas Radeloff ◽  
Mario Ramos Tirado ◽  
Agmal Scherzad ◽  
Rudolf Hagen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zinc Oxide ◽  
Stromal Cells ◽  
Zinc Oxide Nanoparticles ◽  
Caspase 3 ◽  
Cytokine Secretion ◽  
Oxide Nanoparticles ◽  
Zno Nps ◽  
The Impact

Zinc oxide nanoparticles (ZnO-NPs) are widely utilized, for example in manufacturing paints and in the cosmetic industry. In addition, there is raising interest in the application of NPs in stem cell research. However, cytotoxic, genotoxic and pro-inflammatory effects were shown for NPs. The aim of this study was to evaluate the impact of ZnO-NPs on cytokine secretion and differentiation properties of human adipose tissue-derived stromal cells (ASCs). Human ASCs were exposed to the subtoxic concentration of 0.2 µg/mL ZnO-NPs for 24 h. After four weeks of cultivation, adipogenic and osteogenic differentiation procedures were performed. The multi-differentiation potential was confirmed histologically and using polymerase chain reaction (PCR). In addition, the gene expression of IL-6, IL-8, vascular endothelial growth factor (VEGF) and caspase 3 was analyzed. Over the course of four weeks after ZnO-NPs exposure, no significant differences were detected in the gene expression of IL-6, IL-8, VEGF and caspase 3 compared to non-exposed cells. The differentiation was also not affected by the ZnO-NPs. These findings underline the fact, that functionality of ASCs is likely to be unaffected by ZnO-NPs, despite a long-term disposition of NPs in the cells, supposing that the starting concentration was safely in the non-toxic range. This might provide important information for single-use nanomedical applications of ZnO-NPs.

scholarly journals Pathway Analysis Hints Towards Beneficial Effects of Long-Term Vibration on Human Chondrocytes

2018 ◽  
Vol 47 (4) ◽  
pp. 1729-1741 ◽  
Author(s):  
Ronald Lützenberg ◽  
Kendrick Solano ◽  
Christoph Buken ◽  
Jayashree Sahana ◽  
Stefan Riwaldt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Human Chondrocytes ◽  
Cartilage Tissue ◽  
Tunel Staining ◽  
Human Cartilage ◽  
Rhodamine Phalloidin ◽  
The Impact

Background/Aims: Spaceflight negatively influences the function of cartilage tissue in vivo. In vitro human chondrocytes exhibit an altered gene expression of inflammation markers after a two-hour exposure to vibration. Little is known about the impact of long-term vibration on chondrocytes. Methods: Human cartilage cells were exposed for up to 24 h (VIB) on a specialised vibration platform (Vibraplex) simulating the vibration profile which occurs during parabolic flights and compared to static control conditions (CON). Afterwards, they were investigated by phase-contrast microscopy, rhodamine phalloidin staining, microarray analysis, qPCR and western blot analysis. Results: Morphological investigations revealed no changes between CON and VIB chondrocytes. F-Actin staining showed no alterations of the cytoskeleton in VIB compared with CON cells. DAPI and TUNEL staining did not identify apoptotic cells. ICAM-1 was elevated and vimentin, beta-tubulin and osteopontin proteins were significantly reduced in VIB compared to CON cells. qPCR of cytoskeletal genes, ITGB1, SOX3, SOX5, SOX9 did not reveal differential regulations. Microarray analysis detected 13 differentially expressed genes, mostly indicating unspecific stimulations. Pathway analyses demonstrated interactions of PSMD4 and CNOT7 with ICAM. Conclusions: Long-term vibration did not damage human chondrocytes in vitro. The reduction of osteopontin protein and the down-regulation of PSMD4 and TBX15 gene expression suggest that in vitro long-term vibration might even positively influence cultured chondrocytes.

scholarly journals Systemic LPS induces spinal inflammatory gene expression and impairs phrenic long-term facilitation following acute intermittent hypoxia

2013 ◽  
Vol 114 (7) ◽  
pp. 879-887 ◽  
Author(s):  
A. G. Huxtable ◽  
S. M. C. Smith ◽  
S. Vinit ◽  
J. J. Watters ◽  
G. S. Mitchell
Keyword(s):  
Gene Expression ◽  
Systemic Inflammation ◽  
Intermittent Hypoxia ◽  
Neural Control ◽  
Low Grade ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Long Term Facilitation ◽  
The Impact

Although systemic inflammation occurs in most pathological conditions that challenge the neural control of breathing, little is known concerning the impact of inflammation on respiratory motor plasticity. Here, we tested the hypothesis that low-grade systemic inflammation induced by lipopolysaccharide (LPS, 100 μg/kg ip; 3 and 24 h postinjection) elicits spinal inflammatory gene expression and attenuates a form of spinal, respiratory motor plasticity: phrenic long-term facilitation (pLTF) induced by acute intermittent hypoxia (AIH; 3, 5 min hypoxic episodes, 5 min intervals). pLTF was abolished 3 h (vehicle control: 67.1 ± 27.9% baseline; LPS: 3.7 ± 4.2%) and 24 h post-LPS injection (vehicle: 58.3 ± 17.1% baseline; LPS: 3.5 ± 4.3%). Pretreatment with the nonsteroidal anti-inflammatory drug ketoprofen (12.5 mg/kg ip) restored pLTF 24 h post-LPS (55.1 ± 12.3%). LPS increased inflammatory gene expression in the spleen and cervical spinal cord (homogenates and isolated microglia) 3 h postinjection; however, all molecules assessed had returned to baseline by 24 h postinjection. At 3 h post-LPS, cervical spinal iNOS and COX-2 mRNA were differentially increased in microglia and homogenates, suggesting differential contributions from spinal cells. Thus LPS-induced systemic inflammation impairs AIH-induced pLTF, even after measured inflammatory genes returned to normal. Since ketoprofen restores pLTF even without detectable inflammatory gene expression, “downstream” inflammatory molecules most likely impair pLTF. These findings have important implications for many disease states where acute systemic inflammation may undermine the capacity for compensatory respiratory plasticity.

scholarly journals Contrasting effects of different levels of food intake and adiposity on LH secretion and hypothalamic gene expression in sheep

2002 ◽  
Vol 175 (2) ◽  
pp. 383-393 ◽  
Author(s):  
ZA Archer ◽  
SM Rhind ◽  
PA Findlay ◽  
CE Kyle ◽  
L Thomas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Leptin Receptor ◽  
In Situ Hybridisation ◽  
Plasma Concentrations ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Hypothalamic Arcuate Nucleus ◽  
Lh Secretion

Body reserves (long-term) and food intake (short-term) both contribute nutritional feedback to the hypothalamus. Reproductive neuroendocrine output (GnRH/LH) is stimulated by increased food intake and not by high adiposity in sheep, but it is unknown whether appetite-regulating hypothalamic neurons show this differential response. Castrated male sheep (Scottish Blackface) with oestradiol implants were studied in two 4 week experiments. In Experiment 1, sheep were fed to maintain the initial body condition (BC) score of 2.0+/-0.00 (lower BC (LBC), n=7) or 2.9+/-0.09 (higher BC (HBC), n=9), and liveweight of 43+/-1.1 and 59+/-1.6 kg respectively. LBC and HBC sheep had similar mean plasma LH concentration, pulse frequency and amplitude, but HBC animals had higher mean plasma concentrations of insulin (P<0.01), leptin (P<0.01) and glucose (P<0.01). Gene expression (measured by in situ hybridisation) in the hypothalamic arcuate nucleus (ARC) was higher in LBC than HBC sheep for neuropeptide Y (NPY; 486% of HBC, P<0.01), agouti-related peptide (AGRP; 467%, P<0.05) and leptin receptor (OB-Rb; 141%, P<0.05), but lower for cocaine- and amphetamine-regulated transcript (CART; 92%, P<0.05) and similar between groups for pro-opiomelanocortin (POMC). In Experiment 2, sheep with initial mean BC score 2.4+/-0.03 and liveweight 55+/-0.8 kg were fed a liveweight-maintenance ration (low intake, LI, n=7) while sheep with initial mean BC score 2.0+/-0.03 and liveweight 43+/-1.4 kg were fed freely so that BC score increased to 2.5+/-0.00 and liveweight increased to 54+/-1.4 kg (high intake, HI, n=9). Compared with LI, HI sheep had higher mean plasma LH (P<0.05), baseline LH (P<0.01) and pulse amplitude (P<0.01) and showed a trend towards higher pulse frequency. Although there were no differences in final mean plasma concentrations, there were significant increases over time in mean concentrations of insulin (P<0.001), leptin (P<0.05) and glucose (P<0.001) in HI sheep. Gene expression for AGRP in the ARC was higher in HI than LI animals (453% of LI; P<0.05), but expression levels were similar for NPY, OB-Rb, CART and POMC. Thus, the hypothalamus shows differential responses to steady-state adiposity as opposed to an increase in food intake, in terms of both reproductive neuroendocrine activity and hypothalamic appetite-regulating pathways. Differences in hypothalamic gene expression were largely consistent with contemporary levels of systemic leptin and insulin feedback; however, increased nutritional feedback was stimulatory to GnRH/LH whereas constant high feedback was not. The hypothalamus therefore has the ability to retain a nutritional memory that can influence subsequent responses.

scholarly journals The impact of light and temperature on chromatin organization and plant adaptation

2020 ◽  
Vol 71 (17) ◽  
pp. 5247-5255 ◽  
Author(s):  
Giorgio Perrella ◽  
Anna Zioutopoulou ◽  
Lauren R Headland ◽  
Eirini Kaiserli
Keyword(s):  
Gene Expression ◽  
Nuclear Architecture ◽  
Chromatin Organization ◽  
Developmental Trajectory ◽  
Plant Adaptation ◽  
Short And Long Term ◽  
Composition Structure ◽  
The Impact

Abstract Light and temperature shape the developmental trajectory and morphology of plants. Changes in chromatin organization and nuclear architecture can modulate gene expression and lead to short- and long-term plant adaptation to the environment. Here, we review recent reports investigating how changes in chromatin composition, structure, and topology modulate gene expression in response to fluctuating light and temperature conditions resulting in developmental and physiological responses. Furthermore, the potential application of novel revolutionary techniques, such Hi-C, RNA fluorescence in situ hybridization (FISH) and padlock-FISH, to study the impact of environmental stimuli such as light and temperature on nuclear compartmentalization in plants is discussed.

scholarly journals Exploring the impact of complex diseases on non-diseased human tissue transcriptomes

2021 ◽  
Author(s):  
Chi-Lam Poon ◽  
Cho-Yi Chen
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Human Body ◽  
Complex Disease ◽  
Association Studies ◽  
Genetic Effect ◽  
Complex Diseases ◽  
Functional Enrichment ◽  
The Impact

Abstract Background The development of complex diseases is contributed by the combination of multiple factors and complicated interactions between them. Inflammation has recently been associated with many complex diseases and may cause long-term damage to the human body. In this study, we examined whether two types of complex disease systematically altered the transcriptomes of non-diseased human tissues and whether inflammation was linked to identifiable molecular signatures, using post-mortem samples from the Genotype-Tissue Expression (GTEx) project. Results Following a series of differential expression (DE) analyses, dozens to hundreds of DE genes were identified in multiple tissues between subjects with and without a history of cerebrovascular disease (CVD) or major depression (MD). DE genes from these disease-associated tissues—the visceral adipose, tibial artery, caudate, and spinal cord for CVD; and the hypothalamus, putamen, and spinal cord for MD—were further analyzed for functional enrichment. Many pathways associated with immunological events were positively enriched in the DEGs of the CVD-associated tissues, as were the neurological and metabolic pathways in the MD-associated tissues. Eight gene–tissue pairs were found to overlap with those prioritized by our transcriptome-wide association studies (TWAS), indicating a potential genetic effect on gene expression for circulating cytokine phenotypes. Conclusions Complex diseases like CVD and MD may cause observable changes in the gene expression of non-diseased tissues, suggesting that a long-term impact of diseases, lifestyles and environmental factors may together contribute to the appearance of transcriptomic “scars” on the human body. Furthermore, inflammation is probably one of the systemic and long-lasting effects of cerebrovascular events.

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