scholarly journals Postnatal SETD1B is essential for learning and the regulation of neuronal plasticity genes

2021 ◽  
Author(s):  
Alexandra Michurina ◽  
M. Sadman Sakib ◽  
Cemil Kerimoglu ◽  
Dennis Manfred Krueger ◽  
Lalit Kaurani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neuronal Plasticity ◽  
Memory Function ◽  
Rna Seq ◽  
Set Domain ◽  
Postnatal Brain ◽  
Histone 3 ◽  
Expression Of Genes ◽  
Neuronal Gene ◽  
Learning Impairment

Histone 3 lysine 4 methylation (H3K4me) is mediated by six different lysine methyltransferases. Amongst these enzymes SET domain containing 1b (SETD1B) has been linked to syndromic intellectual disability but its role in the postnatal brain has not been studied yet. Here we employ mice that lack Setd1b from excitatory neurons of the postnatal forebrain and combine neuron-specific ChIP-seq and RNA-seq approaches to elucidate its role in neuronal gene expression. We observe that SETD1B controls the expression of genes with a broad H3K4me3 peak at their promoters that represent neuronal enriched genes linked to learning and memory function. Comparative analysis to corresponding data from conditional Kmt2a and Kmt2b knockout mice suggests that this function is specific to SETD1B. Moreover, postnatal loss of Setd1b leads to severe learning impairment, suggesting that SETD1B-mediated regulation of H3K4me levels in postnatal neurons is critical for cognitive function.

scholarly journals SETD1B controls cognitive function via cell type specific regulation of neuronal identity genes

2020 ◽  
Author(s):  
Alexandra Michurina ◽  
Sadman Sakib ◽  
Cemil Kerimoglu ◽  
Dennis Manfred Krüger ◽  
Lalit Kaurani ◽  
...  
Keyword(s):  
Single Cell ◽  
Adult Brain ◽  
Rna Seq ◽  
Set Domain ◽  
Neuronal Identity ◽  
Histone 3 ◽  
Expression Of Genes ◽  
Neuronal Gene ◽  
Cell Type Specific ◽  
Specific Regulation

ABSTRACTHistone-3-lysine-4-methylation (H3K4me) is mediated by six different lysine methyltransferases (KMTs). Amongst these enzymes SET domain containing 1b (SETD1B) has been linked to intellectual disability but its role in the adult brain has not been studied yet. Here we show that mice lacking Setd1b from excitatory neurons of the adult forebrain exhibit severe memory impairment. By combining neuron-specific ChIP-seq, RNA-seq and single cell RNA-seq approaches we show that Setd1b controls the expression of neuronal-identity genes with a broad H3K4me3 peak linked to learning and memory processes. Our data furthermore suggest that basal neuronal gene-expression is ensured by other H3K4 KMTs such as Kmt2a and Kmt2b while the additional presence of Setd1b at the single cell level provides transcriptional consistency to the expression of genes important for learning & memory.

scholarly journals BgeeDB, an R package for retrieval of curated expression datasets and for gene list expression localization enrichment tests

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2748 ◽  
Author(s):  
Andrea Komljenovic ◽  
Julien Roux ◽  
Marc Robinson-Rechavi ◽  
Frederic B. Bastian
Keyword(s):  
Gene Expression ◽  
Gene List ◽  
R Package ◽  
Rna Seq ◽  
Anatomical Structures ◽  
Enrichment Test ◽  
Expression Of Genes ◽  
Affymetrix Microarrays ◽  
New Gene

BgeeDB is a collection of functions to import into R re-annotated, quality-controlled and reprocessed expression data available in the Bgee database. This includes data from thousands of wild-type healthy samples of multiple animal species, generated with different gene expression technologies (RNA-seq, Affymetrix microarrays, expressed sequence tags, and in situ hybridizations). BgeeDB facilitates downstream analyses, such as gene expression analyses with other Bioconductor packages. Moreover, BgeeDB includes a new gene set enrichment test for preferred localization of expression of genes in anatomical structures (“TopAnat”). Along with the classical Gene Ontology enrichment test, this test provides a complementary way to interpret gene lists. Availability: http://www.bioconductor.org/packages/BgeeDB/

scholarly journals Lipid Stores and Lipid Metabolism Associated Gene Expression in Porcine and Bovine Parthenogenetic Embryos Revealed by Fluorescent Staining and RNA-seq

2020 ◽  
Vol 21 (18) ◽  
pp. 6488
Author(s):  
Arkadiusz Kajdasz ◽  
Ewelina Warzych ◽  
Natalia Derebecka ◽  
Zofia E. Madeja ◽  
Dorota Lechniak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Inner Cell Mass ◽  
Mammalian Species ◽  
Cell Mass ◽  
Blastocyst Stage ◽  
Preimplantation Embryos ◽  
Rna Seq ◽  
Expression Of Genes ◽  
Bovine Blastocyst

Compared to other mammalian species, porcine oocytes and embryos are characterized by large amounts of lipids stored mainly in the form of droplets in the cytoplasm. The amount and the morphology of lipid droplets (LD) change throughout the preimplantation development, however, relatively little is known about expression of genes involved in lipid metabolism of early embryos. We compared porcine and bovine blastocyst stage embryos as well as dissected inner cell mass (ICM) and trophoblast (TE) cell populations with regard to lipid droplet storage and expression of genes functionally annotated to selected lipid gene ontology terms using RNA-seq. Comparing the number and the volume occupied by LD between bovine and porcine blastocysts, we have found significant differences both at the level of single embryo and a single blastomere. Aside from different lipid content, we found that embryos regulate the lipid metabolism differentially at the gene expression level. Out of 125 genes, we found 73 to be differentially expressed between entire porcine and bovine blastocyst, and 36 and 51 to be divergent between ICM and TE cell lines. We noticed significant involvement of cholesterol and ganglioside metabolism in preimplantation embryos, as well as a possible shift towards glucose, rather than pyruvate dependence in bovine embryos. A number of genes like DGAT1, CD36 or NR1H3 may serve as lipid associated markers indicating distinct regulatory mechanisms, while upregulated PLIN2, APOA1, SOAT1 indicate significant function during blastocyst formation and cell differentiation in both models.

scholarly journals Congenital Zika syndrome is associated with maternal protein malnutrition

2020 ◽  
Vol 6 (2) ◽  
pp. eaaw6284 ◽  
Author(s):  
J. Barbeito-Andrés ◽  
P. Pezzuto ◽  
L. M. Higa ◽  
A. A. Dias ◽  
J. M. Vasconcelos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Size ◽  
Epidemiological Data ◽  
Protein Malnutrition ◽  
Rna Seq ◽  
Zikv Infection ◽  
Postnatal Brain ◽  
Low Protein ◽  
Congenital Zika Syndrome ◽  
Pregnant Mice

Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS.

scholarly journals Bayesian inference of the gene expression states of single cells from scRNA-seq data

2019 ◽  
Author(s):  
Jérémie Breda ◽  
Mihaela Zavolan ◽  
Erik van Nimwegen
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Single Cells ◽  
Downstream Processing ◽  
Noise Removal ◽  
Rna Seq ◽  
Expression Of Genes ◽  
Normalization Methods ◽  
Quantify Gene Expression ◽  
Selection Of

AbstractIn spite of a large investment in the development of methodologies for analysis of single-cell RNA-seq data, there is still little agreement on how to best normalize such data, i.e. how to quantify gene expression states of single cells from such data. Starting from a few basic requirements such as that inferred expression states should correct for both intrinsic biological fluctuations and measurement noise, and that changes in expression state should be measured in terms of fold-changes rather than changes in absolute levels, we here derive a unique Bayesian procedure for normalizing single-cell RNA-seq data from first principles. Our implementation of this normalization procedure, called Sanity (SAmpling Noise corrected Inference of Transcription activitY), estimates log expression values and associated errors bars directly from raw UMI counts without any tunable parameters.Comparison of Sanity with other recent normalization methods on a selection of scRNA-seq datasets shows that Sanity outperforms other methods on basic downstream processing tasks such as clustering cells into subtypes and identification of differentially expressed genes. More importantly, we show that all other normalization methods present severely distorted pictures of the data. By failing to account for biological and technical Poisson noise, many methods systematically predict the lowest expressed genes to be most variable in expression, whereas in reality these genes provide least evidence of true biological variability. In addition, by confounding noise removal with lower-dimensional representation of the data, many methods introduce strong spurious correlations of expression levels with the total UMI count of each cell as well as spurious co-expression of genes.

scholarly journals Cold-induced lipid dynamics and transcriptional programs in white adipose tissue

BMC Biology ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Ziye Xu ◽  
Wenjing You ◽  
Yanbing Zhou ◽  
Wentao Chen ◽  
Yizhen Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
White Adipose Tissue ◽  
Cold Exposure ◽  
Fatty Acid Elongation ◽  
Rna Seq ◽  
Short Term ◽  
Lipid Dynamics ◽  
Expression Of Genes

Abstract Background In mammals, cold exposure induces browning of white adipose tissue (WAT) and alters WAT gene expression and lipid metabolism to boost adaptive thermogenesis and maintain body temperature. Understanding the lipidomic and transcriptomic profiles of WAT upon cold exposure provides insights into the adaptive changes associated with this process. Results Here, we applied mass spectrometry and RNA sequencing (RNA-seq) to provide a comprehensive resource for describing the lipidomic or transcriptome profiles in cold-induced inguinal WAT (iWAT). We showed that short-term (3-day) cold exposure induces browning of iWAT, increases energy expenditure, and results in loss of body weight and fat mass. Lipidomic analysis shows that short-term cold exposure leads to dramatic changes of the overall composition of lipid classes WAT. Notably, cold exposure induces significant changes in the acyl-chain composition of triacylglycerols (TAGs), as well as the levels of glycerophospholipids and sphingolipids in iWAT. RNA-seq and qPCR analysis suggests that short-term cold exposure alters the expression of genes and pathways involved in fatty acid elongation, and the synthesis of TAGs, sphingolipids, and glycerophospholipids. Furthermore, the cold-induced lipid dynamics and gene expression pathways in iWAT are contrary to those previously observed in metabolic syndrome, neurodegenerative disorders, and aging, suggesting beneficial effects of cold-induced WAT browning on health and lifespan. Conclusion We described the significant alterations in the composition of glyphospholipids, glycerolipids, and sphingolipids and expression of genes involved in thermogenesis, fatty acid elongation, and fatty acid metabolism during the response of iWAT to short-term cold exposure. We also found that some changes in the levels of specific lipid species happening after cold treatment of iWAT are negatively correlated to metabolic diseases, including obesity and T2D.

Cell type-specific endometrial transcriptome changes during initial recognition of pregnancy in the mare

2019 ◽  
Vol 31 (3) ◽  
pp. 496 ◽  
Author(s):  
Iside Scaravaggi ◽  
Nicole Borel ◽  
Rebekka Romer ◽  
Isabel Imboden ◽  
Susanne E. Ulbrich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spatial Information ◽  
Gene Expression Regulation ◽  
Cell Types ◽  
Rna Seq ◽  
Cell Type ◽  
Expression Of Genes ◽  
Prostaglandin F ◽  
Cell Type Specific ◽  
Gene Expression Studies

Previous endometrial gene expression studies during the time of conceptus migration did not provide final conclusions on the mechanisms of maternal recognition of pregnancy (MRP) in the mare. This called for a cell type-specific endometrial gene expression analysis in response to embryo signals to improve the understanding of gene expression regulation in the context of MRP. Laser capture microdissection was used to collect luminal epithelium (LE), glandular epithelium and stroma from endometrial biopsies from Day 12 of pregnancy and Day 12 of the oestrous cycle. RNA sequencing (RNA-Seq) showed greater expression differences between cell types than between pregnant and cyclic states; differences between the pregnant and cyclic states were mainly found in LE. Comparison with a previous RNA-Seq dataset for whole biopsy samples revealed the specific origin of gene expression differences. Furthermore, genes specifically differentially expressed (DE) in one cell type were found that were not detectable as DE in biopsies. Overall, this study revealed spatial information about endometrial gene expression during the phase of initial MRP. The conceptus induced changes in the expression of genes involved in blood vessel development, specific spatial regulation of the immune system, growth factors, regulation of prostaglandin synthesis, transport prostaglandin receptors, specifically prostaglandin F receptor (PTGFR) in the context of prevention of luteolysis.

scholarly journals Activity-Dependent Gene Expression in Neurons

2020 ◽  
pp. 107385842094351
Author(s):  
Philip R. Lee ◽  
R. Douglas Fields
Keyword(s):  
Gene Expression ◽  
Intracellular Signaling ◽  
Action Potential Firing ◽  
Expression Of Genes ◽  
Neuronal Gene ◽  
Potential Firing ◽  
Processing Information ◽  
Subcellular Compartmentation ◽  
Temporal Firing ◽  
Activity Dependent

The function of the nervous system in conveying and processing information necessary to interact with the environment confers unique aspects on how the expression of genes in neurons is regulated. Three salient factors are that (1) neurons are the largest and among the most morphologically complex of all cells, with strict polarity, subcellular compartmentation, and long-distant transport of gene products, signaling molecules, and other materials; (2) information is coded in the temporal firing pattern of membrane depolarization; and (3) neurons must maintain a stable homeostatic level of activation to function so stimuli do not normally drive intracellular signaling to steady state. Each of these factors can require special methods of analysis differing from approaches used in non-neuronal cells. This review considers these three aspects of neuronal gene expression and the current approaches being used to analyze these special features of how the neuronal transcriptome is modulated by action potential firing.

scholarly journals Subgenome Bias and Temporal Postponement of Gene Expression Contributes to the Distinctions of Fiber Quality in Gossypium Species

2021 ◽  
Vol 12 ◽  
Author(s):  
Huan Mei ◽  
Bowen Qi ◽  
Zegang Han ◽  
Ting Zhao ◽  
Menglan Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fiber Quality ◽  
Expression Patterns ◽  
Rna Seq ◽  
Hub Genes ◽  
Hub Gene ◽  
Expression Of Genes ◽  
Multiple Dimensions ◽  
Cotton Species ◽  
Expression Bias

As two cultivated widely allotetraploid cotton species, although Gossypium hirsutum and Gossypium barbadense evolved from the same ancestor, they differ in fiber quality; the molecular mechanism of that difference should be deeply studied. Here, we performed RNA-seq of fiber samples from four G. hirsutum and three G. barbadense cultivars to compare their gene expression patterns on multiple dimensions. We found that 15.90–37.96% of differentially expressed genes showed biased expression toward the A or D subgenome. In particular, interspecific biased expression was exhibited by a total of 330 and 486 gene pairs at 10 days post-anthesis (DPA) and 20 DPA, respectively. Moreover, 6791 genes demonstrated temporal differences in expression, including 346 genes predominantly expressed at 10 DPA in G. hirsutum (TM-1) but postponed to 20 DPA in G. barbadense (Hai7124), and 367 genes predominantly expressed at 20 DPA in TM-1 but postponed to 25 DPA in Hai7124. These postponed genes mainly participated in carbohydrate metabolism, lipid metabolism, plant hormone signal transduction, and starch and sucrose metabolism. In addition, most of the co-expression network and hub genes involved in fiber development showed asymmetric expression between TM-1 and Hai7124, like three hub genes detected at 10 DPA in TM-1 but not until 25 DPA in Hai7124. Our study provides new insights into interspecific expression bias and postponed expression of genes associated with fiber quality, which are mainly tied to asymmetric hub gene network. This work will facilitate further research aimed at understanding the mechanisms underlying cotton fiber improvement.

scholarly journals Parent-of-origin genetic background affects the transcriptional levels of circadian and neuronal plasticity genes following sleep loss

2014 ◽  
Vol 369 (1637) ◽  
pp. 20120471 ◽  
Author(s):  
Federico Tinarelli ◽  
Celina Garcia-Garcia ◽  
Francesco Nicassio ◽  
Valter Tucci
Keyword(s):  
Gene Expression ◽  
Sleep Deprivation ◽  
Neuronal Plasticity ◽  
Genetic Background ◽  
Rebound Effect ◽  
Sleep Loss ◽  
Mouse Strains ◽  
Specific Gene ◽  
Expression Of Genes ◽  
Parent Of Origin

Sleep homoeostasis refers to a process in which the propensity to sleep increases as wakefulness progresses and decreases as sleep progresses. Sleep is tightly organized around the circadian clock and is regulated by genetic and epigenetic mechanisms. The homoeostatic response of sleep, which is classically triggered by sleep deprivation, is generally measured as a rebound effect of electrophysiological measures, for example delta sleep. However, more recently, gene expression changes following sleep loss have been investigated as biomarkers of sleep homoeostasis. The genetic background of an individual may affect this sleep-dependent gene expression phenotype. In this study, we investigated whether parental genetic background differentially modulates the expression of genes following sleep loss. We tested the progeny of reciprocal crosses of AKR/J and DBA/2J mouse strains and we show a parent-of-origin effect on the expression of circadian, sleep and neuronal plasticity genes following sleep deprivation. Thus, we further explored, by in silico , specific functions or upstream mechanisms of regulation and we observed that several upstream mechanisms involving signalling pathways (i.e. DICER1, PKA), growth factors (CSF3 and BDNF) and transcriptional regulators (EGR2 and ELK4) may be differentially modulated by parental effects. This is the first report showing that a behavioural manipulation (e.g. sleep deprivation) in adult animals triggers specific gene expression responses according to parent-of-origin genomic mechanisms. Our study suggests that the same mechanism may be extended to other behavioural domains and that the investigation of gene expression following experimental manipulations should take seriously into account parent-of-origin effects.

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