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Transcriptome-wide survey of mouse CNS-derived cells reveals monoallelic expression within novel gene families.

ABSTRACT: Monoallelic expression is an integral component of regulation of a number of essential genes and gene families. To probe for allele-specific expression in cells of CNS origin, we used next-generation sequencing (RNA-seq) to analyze four clonal neural stem cell (NSC) lines derived from Mus musculus C57BL/6 (B6)×Mus musculus molossinus (JF1) adult female mice. We established a JF1 cSNP library, then ascertained transcriptome-wide expression from B6 vs. JF1 alleles in the NSC lines. Validating the assay, we found that 262 of 268 X-linked genes evaluable in at least one cell line showed monoallelic expression (at least 85% expression of the predominant allele, p-value<0.05). For autosomal genes 170 of 7,198 genes (2.4% of the total) showed monoallelic expression in at least 2 evaluable cell lines. The group included eight known imprinted genes with the expected pattern of allele-specific expression. Among the other autosomal genes with monoallelic expression were five members of the glutathione transferase gene superfamily, which processes xenobiotic compounds as well as carcinogens and cancer therapeutic agents. Monoallelic expression within this superfamily thus may play a functional role in the response to diverse and potentially lethal exogenous factors, as is the case for the immunoglobulin and olfactory receptor superfamilies. Other genes and gene families showing monoallelic expression include the annexin gene family and the Thy1 gene, both linked to inflammation and cancer, as well as genes linked to alcohol dependence (Gabrg1) and epilepsy (Kcnma1). The annotated set of genes will provide a resource for investigation of mechanisms underlying certain cases of these and other major disorders.

SUBMITTER: Li SM

PROVIDER: S-EPMC3285176 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Transcriptome-wide survey of mouse CNS-derived cells reveals monoallelic expression within novel gene families.

Li Sierra M SM Valo Zuzana Z Wang Jinhui J Gao Hanlin H Bowers Chauncey W CW Singer-Sam Judith J

PloS one 20120222 2

Monoallelic expression is an integral component of regulation of a number of essential genes and gene families. To probe for allele-specific expression in cells of CNS origin, we used next-generation sequencing (RNA-seq) to analyze four clonal neural stem cell (NSC) lines derived from Mus musculus C57BL/6 (B6)×Mus musculus molossinus (JF1) adult female mice. We established a JF1 cSNP library, then ascertained transcriptome-wide expression from B6 vs. JF1 alleles in the NSC lines. Validating the ...[more]

PMID: 22384067

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Project description:BACKGROUND:Tendon injuries occur frequently in human and equine athletes. Treatment options are limited, and the prognosis is often poor with functionally deficient scar tissue resulting. Fetal tendon injuries in contrast are capable of healing without forming scar tissue. Embryonic stem cells (ESCs) may provide a potential cellular therapeutic to improve adult tendon regeneration; however, whether they can mimic the properties of fetal tenocytes is unknown. To this end, understanding the unique expression profile of normal adult and fetal tenocytes is crucial to allow validation of ESC-derived tenocytes as a cellular therapeutic. METHODS:Equine adult, fetal and ESC-derived tenocytes were cultured in a three-dimensional environment, with histological, morphological and transcriptomic differences compared. Additionally, the effects on gene expression of culturing adult and fetal tenocytes in either conventional two-dimensional monolayer culture or three-dimensional culture were compared using RNA sequencing. RESULTS:No qualitative differences in three-dimensional tendon constructs generated from adult, fetal and ESCs were found using histological and morphological analysis. However, genome-wide transcriptomic analysis using RNA sequencing revealed that ESC-derived tenocytes' transcriptomic profile more closely resembled fetal tenocytes as opposed to adult tenocytes. Furthermore, this study adds to the growing evidence that monolayer cultured cells' gene expression profiles converge, with adult and fetal tenocytes having only 10 significantly different genes when cultured in this manner. In contrast, when adult and fetal tenocytes were cultured in 3D, large distinctions in gene expression between these two developmental stages were found, with 542 genes being differentially expressed. CONCLUSION:The information provided in this study makes a significant contribution to the investigation into the differences between adult reparative and fetal regenerative cells and supports the concept of using ESC-derived tenocytes as a cellular therapy. Comparing two- and three-dimensional culture also indicates three-dimensional culture as being a more physiologically relevant culture system for determining transcriptomic difference between the same cell types from different developmental stages.

Project description:BackgroundFamilies experiencing high levels of psychological distress are considered a particularly vulnerable population for adverse effects on mental and physical health. Moreover, highly stressed individuals engage less in mental health promoting activities and show low stress management competencies. App-based stress interventions seem promising for the treatment and prevention of stress outcomes and might be a low-threshold solution.ObjectiveThe aim of this study was to identify the requirements for a tailored app to reduce stress in a cohort of highly stressed families that have low stress management skills.MethodsParents (n=1008; age: mean 47.7 years, SD 6.1; female: 599/1008, 59.7%) completed an extensive web-based survey and were subdivided into a target (stressed individuals with low stress competency) and nontarget group according to their reported stress level and stress management competencies. Group differences were analyzed using analysis of variance. In principal component analysis with Kaiser varimax rotation, personally defined stress management goals were grouped into components. Linear regression models were also calculated.ResultsA 3-factor solution cumulatively explained 56% of the variance in personally defined goals of interest for stress management with (1) active strategies (25.61% explained variance), (2) general competency (17.95% explained variance) and (3) passive strategies (12.45% explained variance). The groups differed in age (F1,978=27.67, P<.001), health index (F1,958=246.14, P<.001), personally defined general-competency goal (F1,958=94.16 P<.001), as well as "information acquisition" (F1,971=14.75, P<.001) and "need for stimulation" (F1,981=54.49, P<.001) personality traits. A regression model showed that for the active strategies goals of interest, only app feature information or instructional videos had a significant effect (P=.02). The general competency factor showed none, and the passive strategies factor showed significant effects for 2 app features-suggestions for planning possible activities with the family (P=.01) and diaries for documentation and development of strategies (P=.03).ConclusionsThe results of this survey study highlight the need to develop an app to increase stress management competencies that takes into consideration perceived stress level, stress management skills, personality, and personally defined goals of the user. The content of the app should be tailored to previously detected personality traits, especially selective information acquisition and low need for stimulation. Furthermore, personally defined stress management goals seem to affect interest in some features.

Dataset Information

Transcriptome-wide survey of mouse CNS-derived cells reveals monoallelic expression within novel gene families.

Publications

Transcriptome-wide survey of mouse CNS-derived cells reveals monoallelic expression within novel gene families.

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