Faculty Opinions recommendation of Large-Scale Profiling Reveals the Influence of Genetic Variation on Gene Expression in Human Induced Pluripotent Stem Cells.

2017 ◽  
Author(s):  
Vijay Tiwari ◽  
Hyobin Jeong
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Genetic Variation ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Large Scale ◽  
Induced Pluripotent

scholarly journals Large-Scale Profiling Reveals the Influence of Genetic Variation on Gene Expression in Human Induced Pluripotent Stem Cells

2017 ◽  
Vol 20 (4) ◽  
pp. 533-546.e7 ◽  
Author(s):  
Christopher DeBoever ◽  
He Li ◽  
David Jakubosky ◽  
Paola Benaglio ◽  
Joaquin Reyna ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Genetic Variation ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Large Scale ◽  
Induced Pluripotent

scholarly journals Efficient generation of human primordial germ cell-like cells from pluripotent stem cells in a methylcellulose-based 3D system at large scale

PeerJ ◽  
2019 ◽  
Vol 6 ◽  
pp. e6143 ◽  
Author(s):  
Xiaoman Wang ◽  
Tingting Liao ◽  
Cong Wan ◽  
Xiaoyu Yang ◽  
Jiexiang Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Germ Cell ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Large Scale ◽  
Induction System ◽  
Induced Pluripotent ◽  
In Vitro Induction

Background The mechanisms underlying human germ cell development and infertility remain largely unknown due to bioethical issues and the shortage of experimental materials. Therefore, an effective in vitro induction system of human primordial germ-like cells (hPGCLCs) from human pluripotent stem cells (hPSC) is in high demand. The current strategies used for the generation of hPGCLCs are not only costly but also difficult to perform at a large scale, thereby posing barriers to further research. In this study, we attempted to solve these problems by providing a new 3D culture system for hPGCLC differentiation. Methods The efficiency and relative yield of a methylcellulose (MC)-based 3D hPGCLC induction system were first compared with that of a conventional U96 system. Then, we examined the gene expression of germ cell marker genes and the key epigenetic modifications of the EpCAM-/INTEGRINα6-high cells from the 3D MC induction system and the U96 system via quantitative PCR and immunofluorescence. Finally, the reliability of the MC-based 3D hPGCLC induction system was evaluated via the generation of induced pluripotent stem cells (iPSCs) from the testicular cells of one patient with obstructive azoospermia (OA) and followed by the subsequent differentiation of iPSCs into the germ cell lineage. Results In the present study, we demonstrated that the 3D MC induction system combined with low-cell attachment plates facilitated the generation of hPGCLCs at a large scale. We found that the hPGCLCs generated via the MC system shared similar characteristics to that via the U96 system in terms of the gene expression profiles, germ cell-specific markers, epigenetic modification states and cellular states. In addition, hPGCLCs from iPSCs derived from one OA patient were generated with high efficiency via the present 3D MC induction system. Discussion The in vitro induction of hPGCLCs from human embryonic stem cells (hESCs)/human induced pluripotent stem cells (hiPSCs) has significant implications in exploring the underlying mechanisms of the origin and specification of hPGCs and the epigenetic programming of the human germ line as well as treating male infertility. Here, we developed a simple and efficient 3D induction system to generate hPGCLCs from hESCs/hiPSCs at a large scale, which facilitated the study of human germ cell development and stem cell-based reproductive medicine.

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.

scholarly journals Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression

2012 ◽  
Vol 30 (12) ◽  
pp. 1244-1248 ◽  
Author(s):  
Gabsang Lee ◽  
Christina N Ramirez ◽  
Hyesoo Kim ◽  
Nadja Zeltner ◽  
Becky Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Large Scale ◽  
Familial Dysautonomia ◽  
Induced Pluripotent ◽  
Large Scale Screening
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