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- Khatun, M, et al.
(author)
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Decidualized endometrial stromal cells present with altered androgen response in PCOS
- 2021
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 16287-
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Journal article (peer-reviewed)abstract
- Hyperandrogenic women with PCOS show disrupted decidualization (DE) and placentation. Dihydrotestosterone (DHT) is reported to enhance DE in non-PCOS endometrial stromal cells (eSCCtrl); however, this has not been assessed in PCOS cells (eSCPCOS). Therefore, we studied the transcriptome profile of non-decidualized (non-DE) and DE eSCs from women with PCOS and Ctrl in response to short-term estradiol (E2) and/or progesterone (P4) exposure with/without (±) DHT. The non-DE eSCs were subjected to E2 ± DHT treatment, whereas the DE (0.5 mM 8-Br-cAMP, 96 h) eSCs were post-treated with E2 and P4 ± DHT, and RNA-sequenced. Validation was performed by immunofluorescence and immunohistochemistry. The results showed that, regardless of treatment, the PCOS and Ctrl samples clustered separately. The comparison of DE vs. non-DE eSCPCOS without DHT revealed PCOS-specific differentially expressed genes (DEGs) involved in mitochondrial function and progesterone signaling. When further adding DHT, we detected altered responses for lysophosphatidic acid (LPA), inflammation, and androgen signaling. Overall, the results highlight an underlying defect in decidualized eSCPCOS, present with or without DHT exposure, and possibly linked to the altered pregnancy outcomes. We also report novel factors which elucidate the mechanisms of endometrial dysfunction in PCOS.
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| 4. |
- Katayama, S., et al.
(author)
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Acute wheeze-specific gene module shows correlation with vitamin D and asthma medication
- 2020
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In: European Respiratory Journal. - : NLM (Medline). - 0903-1936 .- 1399-3003. ; 55:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Airway obstruction and wheezing in preschool children with recurrent viral infections are a major clinical problem, and are recognised as a risk factor for the development of chronic asthma. We aimed to analyse whether gene expression profiling provides evidence for pathways that delineate distinct groups of children with wheeze, and in combination with clinical information could contribute to diagnosis and prognosis of disease development. METHODS: We analysed leukocyte transcriptomes from preschool children (6 months-3 years) at acute wheeze (n=107), and at a revisit 2-3 months later, comparing them to age-matched healthy controls (n=66). RNA-sequencing applying GlobinLock was used. The cases were followed clinically until age 7 years. Differential expression tests, weighted correlation network analysis and logistic regression were applied and correlations to 76 clinical traits evaluated. FINDINGS: Significant enrichment of genes involved in the innate immune responses was observed in children with wheeze. We identified a unique acute wheeze-specific gene-module, which was associated with vitamin D levels (p<0.005) in infancy, and asthma medication and FEV1%/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio several years later, at age 7 years (p<0.005). A model that predicts leukotriene receptor antagonist medication at 7 years of age with high accuracy was developed (area under the curve 0.815, 95% CI 0.668-0.962). INTERPRETATION: Gene expression profiles in blood from preschool wheezers predict asthma symptoms at school age, and therefore serve as biomarkers. The acute wheeze-specific gene module suggests that molecular phenotyping in combination with clinical information already at an early episode of wheeze may help to distinguish children who will outgrow their wheeze from those who will develop chronic asthma.
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| 7. |
- Bieder, A, et al.
(author)
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Dyslexia Candidate Gene and Ciliary Gene Expression Dynamics During Human Neuronal Differentiation
- 2020
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In: Molecular neurobiology. - : Springer Science and Business Media LLC. - 1559-1182 .- 0893-7648. ; 57:7, s. 2944-2958
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Journal article (peer-reviewed)abstract
- Developmental dyslexia (DD) is a neurodevelopmental condition with complex genetic mechanisms. A number of candidate genes have been identified, some of which are linked to neuronal development and migration and to ciliary functions. However, expression and regulation of these genes in human brain development and neuronal differentiation remain uncharted. Here, we used human long-term self-renewing neuroepithelial stem (lt-NES, here termed NES) cells derived from human induced pluripotent stem cells to study neuronal differentiation in vitro. We characterized gene expression changes during differentiation by using RNA sequencing and validated dynamics for selected genes by qRT-PCR. Interestingly, we found that genes related to cilia were significantly enriched among upregulated genes during differentiation, including genes linked to ciliopathies with neurodevelopmental phenotypes. We confirmed the presence of primary cilia throughout neuronal differentiation. Focusing on dyslexia candidate genes, 33 out of 50 DD candidate genes were detected in NES cells by RNA sequencing, and seven candidate genes were upregulated during differentiation to neurons, including DYX1C1 (DNAAF4), a highly replicated DD candidate gene. Our results suggest a role of ciliary genes in differentiating neuronal cells and show that NES cells provide a relevant human neuronal model to study ciliary and DD candidate genes.
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