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Transcription profiling by RNA-seq of six African green monkey tissues at different ages (Chlorocebus aethiops sabaeus)

ABSTRACT: Characterization of transcriptomic variation is emerging as a critical tool for understanding how quantitative trait loci (QTL) contribute to complex phenotypes. Human transcriptomic studies are limited by factors such as the feasibility of invasive tissue collection or variable environmental exposures that can be readily overcome in non-human primate (NHP) models. We characterized transcriptomic variation across multiple tissues and developmental stages and between individuals in 59 vervet monkeys from the Vervet Research Colony extended pedigree. We conducted RNA sequencing across early (7, 90 days, and one year) and later (1.25, 1.5, 1.75, 2, 2.5, 3, and 4+ years old) developmental time points in 6 individuals at each stage in five tissue types: two brain tissues from hippocampus and caudate, two endocrine tissues (pituitary and adrenal) and two peripheral tissues serving as a source of biomarkers (blood and fibroblasts)

REANALYSIS of: E-MTAB-4404

ORGANISM(S): Chlorocebus sabaeus

PROVIDER: E-MTAB-4404 | ExpressionAtlas | 2016-09-23

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-MTAB-4404-analysis-methods.tsv	Tabular
	E-MTAB-4404-atlasExperimentSummary.Rdata	Rdata
	E-MTAB-4404-coexpressions.tsv.gz	Tabular
	E-MTAB-4404-configuration.xml	Xml
	E-MTAB-4404-configuration.xml.beforeQC	Xml

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Transcription profiling by RNA-seq of six African green monkey tissues at different ages (Chlorocebus aethiops sabaeus)

Project description:Characterization of transcriptomic variation is emerging as a critical tool for understanding how quantitative trait loci (QTL) contribute to complex phenotypes. Human transcriptomic studies are limited by factors such as the feasibility of invasive tissue collection or variable environmental exposures that can be readily overcome in non-human primate (NHP) models. We characterized transcriptomic variation across multiple tissues and developmental stages and between individuals in 59 vervet monkeys from the Vervet Research Colony extended pedigree. We conducted RNA sequencing across early (7, 90 days, and one year) and later (1.25, 1.5, 1.75, 2, 2.5, 3, and 4+ years old) developmental time points in 6 individuals at each stage in five tissue types: two brain tissues from hippocampus and caudate, two endocrine tissues (pituitary and adrenal) and two peripheral tissues serving as a source of biomarkers (blood and fibroblasts)

2014-02-12 | E-MTAB-4404 | ArrayExpress

Identification of transcript dysregulation in patients with Autism Spectrum Disorders

Project description:In order to unveil the molecular mechanisms at play during the development of autistic brains, we studied cells that are representative of the very early stages of ontogenesis, namely stem cells. We used nasal olfactory stem cells that are readily accessible and can be biopsied safely. We recruited a relatively homogeneous cohort of nine adults with severe autism and low to very low developmental disabilities, and included two more adults with either Asperger syndrome or high-functioning autism, to enlarge the spectrum. The cohort was then paired with 11 age- and gender-matched control individuals. Stem cells were purified, banked and used for a transcriptomic study. Two-colors experiment. The cohort was then paired with 11 age- and gender-matched control individuals. Stem cells were purified, banked and used for a transcriptomic study. Validation by reverse transcription design.

2014-11-22 | E-GEOD-63524 | BioStudies

Hypothalamus-pituitary-gonad axis transcriptome profiling for sex differentiation in Acipenser sinensis.

Project description:Chinese sturgeon (Acipenser sinensis), a critically endangered Acipenseridae family member, is one of the largest anadromous, native fish in China. Numerous research programmes and protection agencies have focused on breeding and preserving this endangered species. However, available information is limited on the different stages of sex development, especially on the reproductive regulation of the hypothalamus-pituitary-gonad (HPG) axis of A. sinensis. To unravel the mechanism of gene interactions during sex differentiation and gonad development of A. sinensis, we performed transcriptome sequencing using HPG samples from male and female A. sinensis in two developmental stages. In this study, 271.19 Gb high-quality transcriptome data were obtained from 45 samples belonging to 15 individuals (six in stage I, six males and three females in stage II). These transcriptomic data will help us understand the reproductive regulation of the HPG axis in the development stages of A. sinensis and provide important reference data for genomic and genetic studies in A. sinensis and related species.

2019-01-01 | S-EPMC6565624 | BioStudies

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis.

Project description:Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT). We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1), collagen type I ? 1 chain (COL1A1), 5'-nucleotidase ecto (NT5E), HtrA serine peptidase 1 (HTRA1) and angiopoietin 1 (ANGPT1) and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

2016-01-01 | S-EPMC5085687 | BioStudies

NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement.

Project description:Background:NKX2-1 related disorders (also known as brain-lung-thyroid syndrome or benign hereditary chorea 1) are associated with a wide spectrum of symptoms. The core features are various movement disorders, characteristically chorea, less frequently myoclonus, dystonia, ataxia; thyroid disease; and lung involvement. The full triad is present in 50% of affected individuals. Numerous additional symptoms may be associated, although many of these were reported only in single cases. Pituitary dysfunction was ambiguously linked to NKX2-1 haploinsufficiency previously. Case Presentation: We examined two members of a family with motor developmental delay, mixed movement disorder (myoclonus, dystonia and chorea) and endocrinological abnormalities (peripheric thyroid disease, and pituitary hormone deficiencies). Dystonia predominated at the father, and myoclonus at the daughter. The father had hypogonadotropic hypogonadism, while the daughter was treated with growth hormone deficiency. Both patients had empty sella on MRI. Candidate gene analyses were negative. Exome sequencing detected a pathogenic stop variation (NM_003317:c.338G>A, p.Trp113*) in the NKX2-1 gene. Conclusions: This case study has two highlights. (1) It draws attention to possible pituitary dysfunction in brain-lung-thyroid syndrome, and provide further evidences that this might be linked to loss of function of the NKX2-1 gene. (2) It underscores the importance of considering NKX2-1 related disorders in the differential diagnosis of myoclonus dystonia.

2018-01-01 | S-EPMC6113386 | BioStudies

Transcriptomic signatures shaped by cell proportions shed light on comparative developmental biology.

Project description:Comparative transcriptomics can answer many questions in developmental and evolutionary developmental biology. Most transcriptomic studies start by showing global patterns of variation in transcriptomes that differ between species or organs through developmental time. However, little is known about the kinds of expression differences that shape these patterns.We compared transcriptomes during the development of two morphologically distinct serial organs, the upper and lower first molars of the mouse. We found that these two types of teeth largely share the same gene expression dynamics but that three major transcriptomic signatures distinguish them, all of which are shaped by differences in the relative abundance of different cell types. First, lower/upper molar differences are maintained throughout morphogenesis and stem from differences in the relative abundance of mesenchyme and from constant differences in gene expression within tissues. Second, there are clear time-shift differences in the transcriptomes of the two molars related to cusp tissue abundance. Third, the transcriptomes differ most during early-mid crown morphogenesis, corresponding to exaggerated morphogenetic processes in the upper molar involving fewer mitotic cells but more migrating cells. From these findings, we formulate hypotheses about the mechanisms enabling the two molars to reach different phenotypes. We also successfully applied our approach to forelimb and hindlimb development.Gene expression in a complex tissue reflects not only transcriptional regulation but also abundance of different cell types. This knowledge provides valuable insights into the cellular processes underpinning differences in organ development. Our approach should be applicable to most comparative developmental contexts.

2017-01-01 | S-EPMC5312534 | BioStudies

Identification of transcript dysregulation in patients with Autism Spectrum Disorders

2014-11-22 | E-GEOD-63524 | ArrayExpress

Gene expression in liver, gill, hypothalamus, pituitary, and olfactory rosettes from Atlantic salmon parr and smolt

Project description:To identify genes involved in the developmental process of Atlantic salmon smoltification, gene expression was compared between smolt and parr in tissues involved in osmoregulation (gill), metabolism (liver), imprinting (olfactory rosettes) and neuroendocrine control (hypothalamus and pituitary). Tissue samples were harvested from laboratory-reared parr and smolts on the same date. Smolts were distinguished from parr by size and appearance; developmental status was confirmed by physiological assays. Eight biological replicates (16 fish) balanced for sex and for dye were used in the liver, gill, olfactory rosette, and hypothalamus comparisons. Four male parr were compared to four male smolts and four female parr were compared to four female smolts; smolts were labeled with Alexa Fluor 555 on four arrays and with Alexa Fluor 647 on four arrays. Six biological replicates (12 fish) were used for the pituitary comparison (two female and four male).

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Biallelic GRM7 variants cause epilepsy, microcephaly, and cerebral atrophy.

Project description:OBJECTIVE:Defects in ion channels and neurotransmitter receptors are implicated in developmental and epileptic encephalopathy (DEE). Metabotropic glutamate receptor 7 (mGluR7), encoded by GRM7, is a presynaptic G-protein-coupled glutamate receptor critical for synaptic transmission. We previously proposed GRM7 as a candidate disease gene in two families with neurodevelopmental disorders (NDDs). One additional family has been published since. Here, we describe three additional families with GRM7 biallelic variants and deeply characterize the associated clinical neurological and electrophysiological phenotype and molecular data in 11 affected individuals from six unrelated families. METHODS:Exome sequencing and family-based rare variant analyses on a cohort of 220 consanguineous families with NDDs revealed three families with GRM7 biallelic variants; three additional families were identified through literature search and collaboration with a clinical molecular laboratory. RESULTS:We compared the observed clinical features and variants of 11 affected individuals from the six unrelated families. Identified novel deleterious variants included two homozygous missense variants (c.2671G>A:p.Glu891Lys and c.1973G>A:p.Arg685Gln) and one homozygous stop-gain variant (c.1975C>T:p.Arg659Ter). Developmental delay, neonatal- or infantile-onset epilepsy, and microcephaly were universal. Three individuals had hypothalamic-pituitary-axis dysfunction without pituitary structural abnormality. Neuroimaging showed cerebral atrophy and hypomyelination in a majority of cases. Two siblings demonstrated progressive loss of myelination by 2 years in both and an acquired microcephaly pattern in one. Five individuals died in early or late childhood. CONCLUSION:Detailed clinical characterization of 11 individuals from six unrelated families demonstrates that rare biallelic GRM7 pathogenic variants can cause DEEs, microcephaly, hypomyelination, and cerebral atrophy.

2020-01-01 | S-EPMC7261753 | BioStudies

Metabolic profiling reveals distinct metabolic alterations in different subtypes of pituitary adenomas and confers therapeutic targets.

Project description:BACKGROUND:Pituitary adenomas are common brain tumors. Although transsphenoidal surgery are able to achieve extensive tumor removal, the rate of recurrence ranges from 5 to 20% depending on the different subtype. Further understanding of these tumors is needed to develop novel strategies to improve the prognosis of patients. But their metabolic characteristics are largely unknown. METHODS:We used metabolomic, transcriptomic, and proteomic approaches to systematically investigate eight subtypes of pituitary adenomas and normal pituitary glands. By blocking IDH2, we investigate IDH2 play an inhibitory role in GH tumor cell growth and tumor secretion. RESULTS:We found that all of the pituitary adenomas displayed downregulated glucose metabolism and glycolysis compared to normal tissues. Together with the differences in amino acids and fatty acids, we categorized these tumors into three clusters. We then re-established the reprogrammed metabolic flux in pituitary adenomas based on multiomic analyses. Take growth hormone-secreting pituitary adenomas as an example, we revealed that IDH2 is a key player in the reprogrammed metabolism of such tumors. By blocking IDH2, we confirmed that IDH2 is a potential target for the inhibition of tumor cell growth and tumor secretion. CONCLUSIONS:Our study first uncovered the metabolic landscape of pituitary adenomas and demonstrated a possible way to inhibit tumor growth by regulating aberrant metabolism.

2019-01-01 | S-EPMC6712670 | BioStudies

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