scholarly journals The gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy are consistent with proposed mechanisms of pathogenesis

2012 ◽  
Vol 3 (5) ◽  
pp. 39 ◽  
Author(s):  
Xiao-Ming Wang ◽  
Wing Yik ◽  
Peilin Zhang ◽  
Wange Lu ◽  
Patricia K Dranchak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Induced Pluripotent

scholarly journals Effect of Small Molecular Compounds on Properties of Fibroblast in Chuan Snub-nosed Monkey

2021 ◽  
Author(s):  
juanjuan wang ◽  
xin liu ◽  
jing yang ◽  
hanxing guo ◽  
jingjing li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cell Morphology ◽  
Pluripotent Stem Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Compound ◽  
Donor Cells ◽  
Induced Pluripotent ◽  
Molecular Compounds

Abstract Small molecular compounds could improve the induction efficiency of induced pluripotent stem cells (iPS). To investigate their effects on the efficiency of interspecies nuclear transfers, fibroblasts from the Chuan snub-nosed monkey were treated with small molecular compounds and used as donor cells to be injected into the enucleated oocytes of a goat. The gene expression profiles in the cell-constructed embryos, with and without the small molecular compound treatments, were determined by qPCR. Results showed that the cell morphology showed obvious changes, while the gene expression profiles of the fibroblasts were altered by the treatment. The pluripotent genes (Oct4, sox2, and nanog) were significantly increased on treatment with the small molecular compounds. Results demonstrated that these small molecular compounds could alter the properties of the donor cells, to promote the expression levels of the pluripotent genes for the Chuan golden-goat interspecies embryo, which would provide references for conservation of Chuan snub-nosed monkey.

Abstract P418: Transcriptomic And Genomic DNA Accessibility Dynamics During Differentiation Of Induced Pluripotent Stem Cells Derived Smooth Muscle Cells And Acquisition Of Contractile Phenotype

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
LU LIU ◽  
Adrien Georges ◽  
Nabila Bouatia-Naji
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Contractile Function ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Human Aorta ◽  
Rna Seq ◽  
Dna Accessibility ◽  
Induced Pluripotent

Introduction: Smooth muscle cells (SMCs) capacity to phenotype switching between proliferative and quiescent (contractile) is a widely studied mechanism in cardiovascular disease. Primary SMCs tend to lose many physiological features in culture, which makes the study of their contractile function challenging. Recently, an optimized protocol of induced pluripotent stem cells (iPSCs) differentiation into contractile SMCs was described. Here we aimed at defining the transcriptomic and open chromatin dynamics during the acquisition of SMCs phenotypes. Methods: We differentiated 4 human iPSC lines (2 males, 2 females) towards either contractile (Repsox induced) or synthetic (PDGF-BB/TGF-β induced) SMC phenotypes using a 24-days protocol. We performed RNA-Seq and assay for transposase accessible chromatin (ATAC)-Seq at 5 time points of differentiation. We analyzed gene expression profiles and compared them to existing dataset of human aorta by principle component analyses (PCA) and gene set enrichment analyses using GO terms. Results: iPSCs derived SMCs showed expected morphology and positive expression of SMC markers. Synthetic SMCs (SSMCs) exhibited greater capacity of proliferation, migration and lower calcium release capacity, compared to contractile SMCs (CSMCs). RNA-Seq results showed that multiple genes involved in the contractile function of arteries, including myosin light chain kinase (MYLK) and angiotensin type 1 receptor ( AGTR1 ) genes were highly expressed in CSMCs compared to SSMCs. Overall, CSMCs conserved SMC properties beyond 24 days and their gene expression profile clustered near human aorta. During late differentiation stages, CSMCs showed an upregulation of genes involved in cardiovascular system development, whereas genes involved in cell stress were upregulated in SSMCs. Conclusions: We describe global genomic profiles of iPSCs derived CSMCs that presented comparable gene expression profiles to mature artery tissue. Combination with upcoming DNA accessibility maps is expected to allow the functional exploration of genetic risk variation involved in several arterial diseases involving the impairment of the SMCs contractile function.

Abstract 12622: The Modeling of Werner Syndrome by Induced Pluripotent Stem Cells

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gakuto Yozu ◽  
Shinsuke Yuasa ◽  
Chikaaki Motoda ◽  
Dai Kusumoto ◽  
Akira Kunitomi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Werner Syndrome ◽  
Expression Profiles ◽  
Global Gene Expression ◽  
Dna Helicase ◽  
Patient Specific ◽  
Induced Pluripotent

Backgrounds: Werner syndrome (WS) is a rare autosomal recessive disorder characterized by premature onset of several aging-associated diseases, such as atherosclerosis, diabetes, cancer, and early death. The aging phenotypes of WS is resembling to those of normal aging. To uncover the mechanism of aging, we tried to model WS by patient-specific induced pluripotent stem cells (iPSCs). WS is caused by mutations in WRN gene belonging to the RecQ DNA helicase family which plays a role in genomic stability. But some of WS phenotypes are hardly explained by genomic instability. Thus, we aimed to model WS by patient-specific iPSCs to elucidate the mechanisms. Methods and Results: We sampled T lymphocytes from a patient with WS. Then we transduced with Yamanaka factors (OCT4, SOX2, KLF4, and MYC) by sendai virus, and iPSC colonies were derived. We confirmed that WS-iPSCs expressed pluripotent markers, could differentiate into all three germ-layer derived tissues, and retained a normal karyotype. We could culture WS-iPSCs over 2 years with pluripotent status. Then, we differentiated WS-iPSCs into fibroblasts-like cells. The proliferation rate of WS-iPSC-derived fibroblast-like cells (WS-iPSC-fibroblasts) was significantly decreased. WS-iPSC-fibroblasts showed a vulnerability to cellular stress and resulted in increased cell population which is positive for senescence associated β-galactosidase activity and γ-H2AX foci. Singled WS-iPSC-fibroblasts showed excessive blebbing of plasma membrane and increased apoptosis compared with control-iPSC-fibroblasts. To compare global gene expression profiles, we performed microarray analysis in WS-iPSC-fibroblasts and control-iPSC-fibroblasts. Interestingly, WS-iPSC-fibroblasts reproduced the global gene expression pattern of physiological aging. To confirm whether the phenotypes of WS-iPSCs are induced by WRN mutation, we generated isogenic control of WS-iPSC (corrected-WS-iPSC) by homologous recombination using helper-dependent adenovirus vector. Corrected-WS-iPSCs lost the aging-associated phenotypes but showed the phenotypes resembling to control-iPSCs. Conclusion: We modeled aging phenotypes by WS-specific iPSCs. This model would be utilize for uncovering the aging mechanisms.

scholarly journals T9. EPIGENETIC PROFILING IN SCHIZOPHRENIA DERIVED HUMAN INDUCED PLURIPOTENT STEM CELLS (HIPSCS) AND NEURONS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S234-S234
Author(s):  
Lorna Farrelly ◽  
Shuangping Zhang ◽  
Erin Flaherty ◽  
Aaron Topol ◽  
Nadine Schrode ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mass Spectrometry ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Neural Progenitor Cells ◽  
Gene Expression Pattern ◽  
Early Gene ◽  
Label Free ◽  
Induced Pluripotent

Abstract Background Schizophrenia (SCZ) is a severe psychiatric disorder affecting ~1% of the world’s population. It is largely heritable with genetic risk reflected by a combination of common variants of small effect and highly penetrant rare mutations. Chromatin modifications are known to play critical roles in the mediation of many neurodevelopmental processes, and, when disturbed, may also contribute to the precipitation of psychiatric disorders, such as SCZ. While a handful of candidate-based studies have measured changes in promoter-bound histone modifications, few mechanistic studies have been carried out to explore how these modifications may affect chromatin to precipitate behavioral phenotypes associated with the disease. Methods We applied an unbiased proteomics approach to evaluate the epigenetic landscape of SCZ in human induced pluripotent stem cells (hiPSC), neural progenitor cells (NPCs) and neurons from SCZ patients vs. matched controls. We utilized proteomics-based, label free liquid chromatography mass spectrometry (LC-MS/MS) on purified histones from these cells and confirmed our results by western blotting in postmortem SCZ cortical brain tissues. Furthermore we validated our findings with the application of histone interaction assays and structural and biophysical assessments to identify and confirm novel chromatin ‘readers’. To relate our findings to a SCZ phenotype we used a SCZ rodent model of prepulse inhibition (PPI) to perform pharmacological manipulations and behavioral assessments. Results Using label free mass spectrometry we performed PTM screening of hiPSCs, NPCs and matured neurons derived from SCZ patients and matched controls. We identified, amongst others, altered patterns of hyperacetylation in SCZ neurons. Additionally we identified enhanced binding of particular acetylation ‘reader’ proteins. Pharmacological inhibition of such proteins in an animal model of amphetamine sensitization ameliorated PPI deficits further validating this epigenetic signature in SCZ. Discussion Recent evidence indicates that relevance and patterns of acetylation in epigenetics advances beyond its role in transcription and small molecule inhibitors of these aberrant interactions hold promise as useful therapeutics. This study identifies a role for modulating gene expression changes associated with a SCZ epigenetic signature and warrants further investigation in terms of how this early gene expression pattern perhaps determines susceptibility or severity of the SCZ disease trajectory.

scholarly journals Preferential gene expression and epigenetic memory of induced pluripotent stem cells derived from mouse pancreas

2015 ◽  
Vol 20 (5) ◽  
pp. 367-381 ◽  
Author(s):  
Daiki Nukaya ◽  
Kohtaro Minami ◽  
Ritsuko Hoshikawa ◽  
Norihide Yokoi ◽  
Susumu Seino
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Epigenetic Memory ◽  
Mouse Pancreas ◽  
Induced Pluripotent

15q11.2 deletion is enriched in patients with total anomalous pulmonary venous connection

2020 ◽  
pp. jmedgenet-2019-106608
Author(s):  
Xiaoliang Li ◽  
Guocheng Shi ◽  
Yang Li ◽  
Xiaoqing Zhang ◽  
Ying Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Mononuclear Cells ◽  
Chromosomal Microarray ◽  
Cardiomyocyte Differentiation ◽  
Induced Pluripotent ◽  
Anomalous Pulmonary Venous Connection ◽  
15Q11.2 Deletion

IntroductionCNV is a vital pathogenic factor of congenital heart disease (CHD). However, few CNVs have been reported for total anomalous pulmonary venous connection (TAPVC), which is a rare form of CHD. Using case-control study, we identified 15q11.2 deletion associated with TAPVC. We then used a TAPVC trio as model to reveal possible molecular basis of 15q11.2 microdeletion.MethodsCNVplex and Chromosomal Microarray were used to identify and validate CNVs in samples from 231 TAPVC cases and 200 healthy controls from Shanghai Children’s Medical Center. In vitro cardiomyocyte differentiation of induced pluripotent stem cells from peripheral blood mononuclear cells for a TAPVC trio with paternal inherited 15q11.2 deletion was performed to characterise the effect of the deletion on cardiomyocyte differentiation and gene expression.ResultsThe 15q11.2 microdeletion was significantly enriched in patients with TAPVC compared with healthy control (13/231 in patients vs 0/200 in controls, p=5.872×10−2, Bonferroni adjusted) using Fisher’s exact test. Induced pluripotent stem cells from the proband could not differentiate into normal cardiomyocyte. Transcriptomic analysis identified a number of differentially expressed genes in the 15q11.2 deletion carriers of the family. TAPVC disease-causing genes such as PITX2, NKX2-5 and ANKRD1 showed significantly higher expression in the proband compared with her healthy mother. Knockdown of TUBGCP5 could lead to abnormal cardiomyocyte differentiation.ConclusionWe discovered that the 15q11.2 deletion is significantly associated with TAPVC. Gene expression profile that might arise from 15q11.2 deletion for a TAPVC family was characterised using cell experiments.

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