scholarly journals Olfactory bulb astrocytes mediate sensory circuit processing through Sox9 in the mouse brain

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kevin Ung ◽  
Teng-Wei Huang ◽  
Brittney Lozzi ◽  
Junsung Woo ◽  
Elizabeth Hanson ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Sensory Processing ◽  
Neuronal Development ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Adult Brain ◽  
Sensory Function ◽  
Sensory Response ◽  
Sequencing Analysis ◽  
Functional Changes

AbstractThe role of transcription factors during astrocyte development and their subsequent effects on neuronal development has been well studied. Less is known about astrocytes contributions towards circuits and behavior in the adult brain. Astrocytes play important roles in synaptic development and modulation, however their contributions towards neuronal sensory function and maintenance of neuronal circuit architecture remain unclear. Here, we show that loss of the transcription factor Sox9 results in both anatomical and functional changes in adult mouse olfactory bulb (OB) astrocytes, affecting sensory processing. Indeed, astrocyte-specific deletion of Sox9 in the OB results in decreased odor detection thresholds and discrimination and it is associated with aberrant neuronal sensory response maps. At functional level, loss of astrocytic Sox9 impairs the electrophysiological properties of mitral and tufted neurons. RNA-sequencing analysis reveals widespread changes in the gene expression profiles of OB astrocytes. In particular, we observe reduced GLT-1 expression and consequential alterations in glutamate transport. Our findings reveal that astrocytes are required for physiological sensory processing and we identify astrocytic Sox9 as an essential transcriptional regulator of mature astrocyte function in the mouse OB.

Abstract 268: Strain-specific Cardiac Fibroblast Response to Isoproterenol-induced Cardiac Fibrosis

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Shuin Park ◽  
Sara Ranjbarvaziri ◽  
Fides Lay ◽  
Peng Zhao ◽  
Aldons J Lusis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Expression Profiles ◽  
Inbred Mouse ◽  
Gene Expression Profiles ◽  
Mouse Strains ◽  
Sequencing Analysis ◽  
Different Strains

Fibroblasts are a heterogeneous population of cells that function within the injury response mechanisms across various tissues. Despite their importance in pathophysiology, the effects of different genetic backgrounds on fibroblast contribution to the development of disease has yet to be addressed. It has previously been shown that mice in the Hybrid Mouse Diversity Panel, which consists of 110 inbred mouse strains, display a spectrum in severity of cardiac fibrosis in response to chronic treatment of isoproterenol (ISO). Here, we characterized cardiac fibroblasts (CFbs) from three different mouse strains (C57BL/6J, C3H/HeJ, and KK/HIJ) which exhibited varying degrees of fibrosis after ISO treatment. The select strains of mice underwent sham or ISO treatment via intraperitoneally-implanted osmotic pumps for 21 days. Masson’s Trichrome staining showed significant differences in fibrosis in response to ISO, with KK/HIJ mice demonstrating the highest levels, C3H/HeJ exhibiting milder levels, and C57BL/6J demonstrating little to no fibrosis. When CFbs were isolated and cultured from each strain, the cells demonstrated similar traits at the basal level but responded to ISO stimuli in a strain-specific manner. Likewise, CFbs demonstrated differential behavior and gene expression in vivo in response to ISO. ISO treatment caused CFbs to proliferate similarly across all strains, however, immunofluorescence staining showed differential levels of CFb activation. Additionally, RNA-sequencing analysis revealed unique gene expression profiles of all three strains upon ISO treatment. Our study depicts the phenotypic heterogeneity of CFbs across different strains of mice and our results suggest that ISO-induced cardiac fibrosis is a complex process that is independent of fibroblast proliferation and is mainly driven by the activation/inhibition of genes involved in pro-fibrotic pathways.

The postpartum endometrial inflammatory response: a normal physiological event with potential implications for bovine fertility

2012 ◽  
Vol 24 (8) ◽  
pp. 1028 ◽  
Author(s):  
Aspinas Chapwanya ◽  
Kieran G. Meade ◽  
Cathriona Foley ◽  
Fernando Narciandi ◽  
Alexander C. O. Evans ◽  
...  
Keyword(s):  
Acute Phase Protein ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
High Power Field ◽  
Inflammatory Gene Expression ◽  
Functional Changes ◽  
Severe Inflammation ◽  
Uterine Involution ◽  
Bovine Fertility ◽  
Key Events

After calving, the bovine endometrium undergoes marked morphological and functional changes that are necessary for subsequent re-breeding. Regulation and integration of these key events are largely uncharacterised. Here, endometrial swabs and biopsies were taken at 15, 30 and 60 days postpartum (DPP) from 13 healthy primiparous cows, 10 of which subsequently conceived, with a view to characterising innate and inflammatory gene expression profiles. Endometrial biopsies exhibited severe inflammation (>75 leukocytes per high-power field) at 15 DPP, which had begun to resolve by 30 DPP and had completely resolved by 60 DPP. The severe inflammation at 15 DPP coincided with uterine infection in all cows and a significant increase (P < 0.05) in the expression of all of 16 genes investigated, including CD45, IL8, IL6, IL1, TNF, TAP, SAA3 and HP at 15 DPP, relative to 60 DPP. All of these parameters had begun to return to normal physiological levels at 30 DPP. Systemically, serum protein concentrations of IL-8 were elevated at 15 DPP compared with 60 DPP (78 pg mL–1 vs 48 pg mL–1; P = 0.02). These results indicate that endometrial inflammation, leukocyte infiltration and increased expression of pro-inflammatory, antimicrobial and acute-phase protein genes are expected features of the postpartum period, critical to bacterial clearance and uterine involution.

Postnatal Neurogenesis in the Olfactory Bulb

2016 ◽  
Author(s):  
Aleksandra Polosukhina ◽  
Pierre-Marie Lledo
Keyword(s):  
Olfactory Bulb ◽  
Granule Cells ◽  
Sensory Information ◽  
Adult Brain ◽  
Sensory Function ◽  
The Other ◽  
Forthcoming Article ◽  
Adult Born Neurons ◽  
Newborn Neurons ◽  
The Brain

This is an advance summary of a forthcoming article in the Oxford Research Encyclopedia of Neuroscience. Please check back later for the full article. In adult mammals, the olfactory bulb and the hippocampus are the regions in the brain that undergo continuous neurogenesis (production and recruitment of newborn neurons). While the other regions of the brain still retain a certain degree of plasticity after birth, they no longer can integrate new neurons. In rodents, thousands of adult-born neurons integrate into the bulb each day, and this process has been found to contribute not only to sensory function, but also to olfactory memory. This was a surprising finding, since historically the adult-brain has been viewed as a static organ. Understanding the process of regeneration of mature neurons in the brain has great potential for therapeutic applications. Consequently, this process of adult-neurogenesis has received widespread attention from clinicians and scientists. Neuroblasts bound for the olfactory bulb are produced in the subventricular zone of the lateral ventricle. Once they reach the olfactory bulb, they mostly develop into inhibitory interneurons called granule cells. Just after one month, about half of the adult-born neurons are eliminated, and the other half fully integrate and function in the olfactory bulb. These cells not only process information from the sensory neurons in the bulb, but also receive massive innervation from various regions of the brain, including the olfactory cortex, locus coeruleus, the horizontal limb of diagonal band of Broca, and the dorsal raphe nucleus. The sensory (bottom-up) and cortical (top-down) activity has been found to play a vital role in the adult-born granule cell survival. Though the exact purpose of these newborn neurons has not been identified, some emerging functions include maintenance of olfactory bulb circuitry, modulating sensory information, modulating olfactory learning, and memory.

scholarly journals Single-Cell Transcriptome Analysis Profile of Meniscal Tissue Macrophages in Human Osteoarthritis

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Jingbin Zhou ◽  
Zhihong Zhao ◽  
Chen He ◽  
Feng Gao ◽  
Yu Guo ◽  
...  
Keyword(s):  
Single Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Vital Role ◽  
Low Grade ◽  
Sequencing Analysis ◽  
Human Knee ◽  
Meniscal Tissue ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Osteoarthritis (OA) has long been considered as a degenerative disease, but growing evidence suggests that inflammation plays a vital role in its pathogenesis. Unlike rheumatoid arthritis and other autoimmune diseases, inflammation in OA is chronic and, in relatively low grade, mainly mediated by the innate immune system, especially macrophages. However, due to its low abundance, there is a lack of systematic studies on macrophages in the OA condition. Here, we have used single-cell RNA sequencing analysis to gain insight into the heterogeneity and functional specialization of human knee macrophages. We also compared the gene expression profiles of macrophages in healthy people and OA patients and found the characteristic changes of special macrophages in the OA knee. We believe that this in-depth understanding of the basis of OA inflammation will bring hope for the development of new therapies.

Differential gene expression profiles of the olfactory bulb after nasal obstruction in neonatal rats

2008 ◽  
Vol 138 (5) ◽  
pp. 648-654 ◽  
Author(s):  
Gan-Undram Semjidsuren ◽  
Gi Jung Im ◽  
Sang Hag Lee ◽  
Se Jin Park ◽  
Ho Yeon Hwang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Olfactory Bulb ◽  
Differential Gene Expression ◽  
Nasal Obstruction ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Neonatal Rats ◽  
Differential Gene

scholarly journals Development of Functional Connectome Gradients during Childhood and Adolescence

2021 ◽  
Author(s):  
Yunman Xia ◽  
Mingrui Xia ◽  
Jin Liu ◽  
Xuhong Liao ◽  
Tianyuan Lei ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Normal Development ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Brain Network ◽  
Adult Brain ◽  
Childhood And Adolescence ◽  
Imaging Data ◽  
Cognitive Growth ◽  
Magnetic Resonance Imaging Data

Connectome mapping studies have documented a principal primary-to-transmodal gradient in the adult brain network, capturing a functional spectrum which ranges from perception and action to abstract cognition. However, how this gradient pattern develops and whether its development is linked to cognitive growth, topological reorganization, and gene expression profiles remain largely unknown. Using longitudinal resting-state functional magnetic resonance imaging data from 305 children (ages 6-14), we describe substantial changes in the primary-to-transmodal gradient between childhood and adolescence, including emergence as the principal gradient, expansion of global topography, and focal tuning in primary and default-mode regions. These gradient changes are mediated by developmental changes in network integration and segregation, and are associated with abstract processing functions such as working memory and expression levels of calcium ion regulated exocytosis, synaptic transmission, and axon and synapse part related genes. Our findings have implications for understanding connectome maturation principles in normal development and developmental disorders.

scholarly journals Suppression of DSB Formation by Polβ in Active DNA Demethylation is Required for Postnatal Hippocampal Development

2019 ◽  
Author(s):  
Akiko Uyeda ◽  
Kohei Onishi ◽  
Teruyoshi Hirayama ◽  
Satoko Hattori ◽  
Tsuyoshi Miyakawa ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Hippocampal Neurons ◽  
Genome Stability ◽  
Neuronal Development ◽  
Excision Repair ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Dna Demethylation ◽  
Spatial Learning And Memory ◽  
Active Dna Demethylation

AbstractGenome stability is essential for brain development and function. However, the contribution of DNA repair to genome stability in neurons remains elusive. Here, we demonstrate that the base excision repair protein Polβ is involved in hippocampal neuronal differentiation via a TET-mediated active DNA demethylation during early postnatal stages. Polβ deficiency induced extensive DNA double-strand breaks (DSBs) in hippocampal neurons, and a lesser extent in cortical neurons, during a period in which decreased levels of 5-methylcytosine were observed in genomic DNA. Inhibition of the hydroxylation of 5-methylcytosine by microRNAs miR29a/b-1 expression diminished DSB formation. Conversely, its induction by TET1 overexpression increased DSBs. The damaged hippocampal neurons exhibited aberrant neuronal gene expression profiles and dendrite formation. Behavioral analyses revealed impaired spatial learning and memory in adulthood. Thus, Polβ maintains genome stability in the active DNA demethylation that occurs during postnatal neuronal development, thereby contributing to differentiation and subsequent behavior.

scholarly journals Subtle left-right asymmetry of gene expression profiles in embryonic and foetal human brains

2018 ◽  
Author(s):  
Carolien G.F. de Kovel ◽  
Steven N. Lisgo ◽  
Simon E. Fisher ◽  
Clyde Francks
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Adult Brain ◽  
Human Embryos ◽  
Sequencing Data ◽  
Brain Organization ◽  
Central Nervous Systems ◽  
Left Right Asymmetry ◽  
Human Brains

AbstractLeft-right laterality is an important aspect of human brain organization for which the genetic basis is poorly understood. Using RNA sequencing data we contrasted gene expression in left- and right-sided samples from several structures of the anterior central nervous systems of post mortem human embryos and fetuses. While few individual genes stood out as significantly lateralized, most structures showed evidence of laterality of their overall transcriptomic profiles. These left-right differences showed overlap with age-dependent changes in expression, indicating lateralized maturation rates, but not consistently in left-right orientation over all structures. Brain asymmetry may therefore originate in multiple locations, or if there is a single origin, it is earlier than 5 weeks post conception, with structure-specific lateralized processes already underway by this age. This pattern is broadly consistent with the weak correlations reported between various aspects of adult brain laterality, such as language dominance and handedness.

scholarly journals Upregulation of cancer-associated gene expression in activated fibroblasts in a mouse model of non-alcoholic steatohepatitis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Masahiro Asakawa ◽  
Michiko Itoh ◽  
Takayoshi Suganami ◽  
Takeru Sakai ◽  
Sayaka Kanai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Xenograft Model ◽  
Gene Expression Profiles ◽  
Sequencing Analysis ◽  
Alcoholic Steatohepatitis ◽  
Activated Fibroblasts

AbstractNon-alcoholic steatohepatitis (NASH), characterized by chronic inflammation and fibrosis, is predicted to be the leading cause of cirrhosis and hepatocellular carcinoma (HCC) in the next decade. Although recent evidence suggests the importance of fibrosis as the strongest determinant of HCC development, the molecular mechanisms underlying NASH-induced carcinogenesis still remain unclear. Here we performed RNA sequencing analysis to compare gene expression profiles of activated fibroblasts prepared from two distinct liver fibrosis models: carbon tetrachloride–induced fibrosis as a model without obesity and HCC and genetically obese melanocortin 4 receptor–deficient (MC4R-KO) mice fed Western diet, which develop steatosis, NASH, and eventually HCC. Our data showed that activated fibroblasts exhibited distinct gene expression patterns in each etiology, and that the ‘pathways in cancer’ were selectively upregulated in the activated fibroblasts from MC4R-KO mice. The most upregulated gene in these pathways was fibroblast growth factor 9 (FGF9), which was induced by metabolic stress such as palmitate. FGF9 exerted anti-apoptotic and pro-migratory effects in fibroblasts and hepatoma cells in vitro and accelerated tumor growth in a subcutaneous xenograft model. This study reveals upregulation of cancer-associated gene expression in activated fibroblasts in NASH, which would contribute to the progression from NASH to HCC.

scholarly journals Gene expression profiles of dicyemid life-cycle stages may explain how dispersing larvae locate new hosts

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Tsai-Ming Lu ◽  
Hidetaka Furuya ◽  
Noriyuki Satoh
Keyword(s):  
Gene Expression ◽  
Life Cycle ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Transport ◽  
Complex Life Cycle ◽  
Sensory Response ◽  
Specific Gene ◽  
Life Cycle Stages ◽  
New Hosts

Abstract Metazoans have evolved a great variety of life histories in response to environmental conditions. A unique example is encountered in dicyemid mesozoans. In addition to a highly simplified adult body comprising only ~ 30 cells, dicyemids exhibit a parasitic lifestyle that includes nematogens (asexual reproductive adults), rhombogens (sexual reproductive adults), vermiform larvae generated by nematogens, and infusoriform larvae generated by rhombogens. However, due to the difficulties of observing microscopic endoparasites, the complex life cycle and biological functions of life-cycle stages of dicyemids have remained mysterious. Taking advantage of the recently decoded genome of Dicyema japonicum, we examined genes that undergird this lifestyle. Using stage-specific gene expression profiles, we found that biological processes associated with molecular transport, developmental regulation, and sensory response are specified at different stages. Together with the expression of potential neurotransmitters, we further suggest that apical cells in infusoriform larva probably serve sensory functions, although dicyemids have no nervous system. Gene expression profiles show that more genes are expressed in free-living infusoriform larvae than in the other three stages, and that some of these genes are likely involved in locating new hosts. These data provide molecular information about the unique lifestyle of dicyemids and illustrate how an extremely simplified endoparasite adapted and retained gene sets and morphological characters to complete its life cycle.

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