scholarly journals Reprogramming of EBV-immortalized B-lymphocyte cell lines into induced pluripotent stem cells

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1801-1805 ◽  
Author(s):  
Su Mi Choi ◽  
Hua Liu ◽  
Pooja Chaudhari ◽  
Yonghak Kim ◽  
Linzhao Cheng ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
B Lymphocyte ◽  
Disease Modeling ◽  
Genetic Disorders ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Inherited Disease ◽  
Induced Pluripotent ◽  
Lymphocyte Cell

AbstractEBV-immortalized B lymphocyte cell lines have been widely banked for studying a variety of diseases, including rare genetic disorders. These cell lines represent an important resource for disease modeling with the induced pluripotent stem cell (iPSC) technology. Here we report the generation of iPSCs from EBV-immortalized B-cell lines derived from multiple inherited disease patients via a nonviral method. The reprogramming method for the EBV cell lines involves a distinct protocol compared with that of patient fibroblasts. The B-cell line–derived iPSCs expressed pluripotency markers, retained the inherited mutation and the parental V(D)J rearrangement profile, and differentiated into all 3 germ layer cell types. There was no integration of the reprogramming-related transgenes or the EBV-associated genes in these iPSCs. The ability to reprogram the widely banked patient B-cell lines will offer an unprecedented opportunity to generate human disease models and provide novel drug therapies.

scholarly journals Tracing Early Neurodevelopment in Schizophrenia with Induced Pluripotent Stem Cells

Cells ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 140 ◽  
Author(s):  
Ruhel Ahmad ◽  
Vincenza Sportelli ◽  
Michael Ziller ◽  
Dietmar Spengler ◽  
Anke Hoffmann
Keyword(s):  
Disease Modeling ◽  
Sense Of Self ◽  
Early Adulthood ◽  
Neuronal Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Micro Rna ◽  
Patient Specific ◽  
Induced Pluripotent

Schizophrenia (SCZ) is a devastating mental disorder that is characterized by distortions in thinking, perception, emotion, language, sense of self, and behavior. Epidemiological evidence suggests that subtle perturbations in early neurodevelopment increase later susceptibility for disease, which typically manifests in adolescence to early adulthood. Early perturbations are thought to be significantly mediated through incompletely understood genetic risk factors. The advent of induced pluripotent stem cell (iPSC) technology allows for the in vitro analysis of disease-relevant neuronal cell types from the early stages of human brain development. Since iPSCs capture each donor’s genotype, comparison between neuronal cells derived from healthy and diseased individuals can provide important insights into the molecular and cellular basis of SCZ. In this review, we discuss results from an increasing number of iPSC-based SCZ/control studies that highlight alterations in neuronal differentiation, maturation, and neurotransmission in addition to perturbed mitochondrial function and micro-RNA expression. In light of this remarkable progress, we consider also ongoing challenges from the field of iPSC-based disease modeling that call for further improvements on the generation and design of patient-specific iPSC studies to ultimately progress from basic studies on SCZ to tailored treatments.

Transcriptome Profiling Reveals Degree of Variability in Induced Pluripotent Stem Cell Lines: Impact for Human Disease Modeling

2015 ◽  
Vol 17 (5) ◽  
pp. 327-337 ◽  
Author(s):  
Jens Schuster ◽  
Jonatan Halvardson ◽  
Laureanne Pilar Lorenzo ◽  
Adam Ameur ◽  
Maria Sobol ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Human Disease ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Transcriptome Profiling ◽  
Stem Cell Lines ◽  
Induced Pluripotent

Functional Analysis of PTH1R Variants Found in Primary Failure of Eruption

2020 ◽  
Vol 99 (4) ◽  
pp. 429-436
Author(s):  
E. Izumida ◽  
T. Suzawa ◽  
Y. Miyamoto ◽  
A. Yamada ◽  
M. Otsu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Disease Modeling ◽  
Lentiviral Vector ◽  
Genetic Disorders ◽  
Induced Pluripotent Stem Cell ◽  
Osteoblastic Differentiation ◽  
Bone Morphogenetic Protein 2 ◽  
Primary Failure Of Eruption ◽  
Key Factor ◽  
Induced Pluripotent

Although many variants of the parathyroid hormone 1 receptor (PTH1R) gene are known to be associated with primary failure of eruption (PFE), the mechanisms underlying the link remains poorly understood. We here performed functional analyses of PTH1R variants reported in PFE patients—namely, 356C>T (P119L), 395C>T (P132L), 439C>T (R147C), and 1148G>A (R383Q)—using HeLa cells with a lentiviral vector-mediated genetic modification. Two particular variants, P119L and P132L, had severe reduction in a level of N-linked glycosylation when compared with wild-type PTH1R, whereas the other 2 showed modest alteration. PTH1R having P119L or P132L showed marked decrease in the affinity to PTH1-34, which likely led to severely impaired cAMP accumulation upon stimulation in cells expressing these mutants, highlighting the importance of these 2 amino acid residues for ligand-mediated proper functioning of PTH1R. To further gain insights into PTH1R functions, we established the induced pluripotent stem cell (iPSC) lines from a patient with PFE and the heterozygous P132L mutation. When differentiated into osteoblastic-lineage cells, PFE-iPSCs showed no abnormality in mineralization. The mRNA expression of RUNX2, SP7, and BGLAP, the osteoblastic differentiation-related genes, and that of PTH1R were augmented in both PFE-iPSC-derived cells and control iPSC-derived cells in the presence of bone morphogenetic protein 2. Also, active vitamin D3 induced the expression of RANKL, a major key factor for osteoclastogenesis, equally in osteoblastic cells derived from control and PFE-iPSCs. In sharp contrast, exposure to PTH1-34 resulted in no induction of RANKL mRNA expression in the cells expressing P132L variant PTH1R, consistent with the idea that a type of heterozygous PTH1R gene mutation would spoil PTH-dependent response in osteoblasts. Collectively, this study demonstrates a link between PFE-associated genetic alteration and causative functional impairment of PTH1R, as well as a utility of iPSC-based disease modeling for future elucidation of pathogenesis in genetic disorders, including PFE.

scholarly journals Hepatitis C virus core protein expression in human B-cell lines does not significantly modify main proliferative and apoptosis pathways

2002 ◽  
Vol 83 (7) ◽  
pp. 1665-1671 ◽  
Author(s):  
Carlo Giannini ◽  
Patrizio Caini ◽  
Francesca Giannelli ◽  
Francesca Fontana ◽  
Dina Kremsdorf ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Cell Lines ◽  
B Lymphocyte ◽  
Core Protein ◽  
Hcv Core Protein ◽  
Lymphocyte Cell

Hepatitis C virus (HCV) chronic infection has been associated with many lymphoproliferative disorders. Several studies performed on hepatoma and fibroblast cell lines suggest a role of the HCV core protein in activation of cellular transduction pathways that lead to cell proliferation and inhibition of apoptosis. However, no data are available concerning the effects of HCV core expression on B-lymphocyte proliferation and apoptosis. B-lymphocyte cell lines permanently expressing full-length HCV 1b core sequences isolated from chronically infected patients were established using B-cell lines at different degrees of differentiation. Clones and pools of clones permanently expressing the HCV core were selected and characterized for protein expression by Western blot and FACS. Expression of HCV core proteins did not significantly enhance cell proliferation rates under normal culture conditions or under mitogenic stimulation. Analysis of NF-κB, CRE, TRE and SRE pathways by luciferase reporter genes did not show a significant influence of HCV core expression on these signal transduction cascades in B-lymphocytes. The effects of HCV core on anti-IgM and anti-FAS-induced apoptosis in B-cell lines was also analysed. In this experimental model, HCV core expression did not significantly modify the apoptotic profile of the B-lymphocyte cell lines tested. These data underline a cell type-specific effect of HCV core expression. In fact, it was not possible to show a significant contribution of the HCV core protein in activation of the major B-cell signal transduction pathways involved in the regulation of proliferation and programmed cell death, which is in contrast with the results reported in hepatoma cell lines.

scholarly journals Multicellular Human Cardiac Organoids Transcriptomically Model Distinct Tissue-Level Features of Adult Myocardium

2021 ◽  
Vol 22 (16) ◽  
pp. 8482
Author(s):  
Charles M. Kerr ◽  
Dylan Richards ◽  
Donald R. Menick ◽  
Kristine Y. Deleon-Pennell ◽  
Ying Mei
Keyword(s):  
Immune Cells ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Tissue Level ◽  
In Vitro Models ◽  
Human Myocardium ◽  
Expression Of Genes ◽  
Induced Pluripotent

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used for disease modeling and drug cardiotoxicity screening. To this end, we recently developed human cardiac organoids (hCOs) for modeling human myocardium. Here, we perform a transcriptomic analysis of various in vitro hiPSC-CM platforms (2D iPSC-CM, 3D iPSC-CM and hCOs) to deduce the strengths and limitations of these in vitro models. We further compared iPSC-CM models to human myocardium samples. Our data show that the 3D in vitro environment of 3D hiPSC-CMs and hCOs stimulates the expression of genes associated with tissue formation. The hCOs demonstrated diverse physiologically relevant cellular functions compared to the hiPSC-CM only models. Including other cardiac cell types within hCOs led to more transcriptomic similarities to adult myocardium. hCOs lack matured cardiomyocytes and immune cells, which limits a complete replication of human adult myocardium. In conclusion, 3D hCOs are transcriptomically similar to myocardium, and future developments of engineered 3D cardiac models would benefit from diversifying cell populations, especially immune cells.

Molecular Profiling of Human Induced Pluripotent Stem Cell-Derived Cells and their Application for Drug Safety Study

2020 ◽  
Vol 21 (9) ◽  
pp. 807-828
Author(s):  
Toshikatsu Matsui ◽  
Norimasa Miyamoto ◽  
Fumiyo Saito ◽  
Tadahiro Shinozawa
Keyword(s):  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Drug Candidate ◽  
Drug Induced ◽  
Differentiated Cells ◽  
Potential Applicability ◽  
Post Marketing ◽  
Induced Pluripotent ◽  
Human Ipsc

Drug-induced toxicity remains one of the leading causes of discontinuation of the drug candidate and post-marketing withdrawal. Thus, early identification of the drug candidates with the potential for toxicity is crucial in the drug development process. With the recent discovery of human- Induced Pluripotent Stem Cells (iPSC) and the establishment of the differentiation protocol of human iPSC into the cell types of interest, the differentiated cells from human iPSC have garnered much attention because of their potential applicability in toxicity evaluation as well as drug screening, disease modeling and cell therapy. In this review, we expanded on current information regarding the feasibility of human iPSC-derived cells for the evaluation of drug-induced toxicity with a focus on human iPSCderived hepatocyte (iPSC-Hep), cardiomyocyte (iPSC-CMs) and neurons (iPSC-Neurons). Further, we CSAHi, Consortium for Safety Assessment using Human iPS Cells, reported our gene expression profiling data with DNA microarray using commercially available human iPSC-derived cells (iPSC-Hep, iPSC-CMs, iPSC-Neurons), their relevant human tissues and primary cultured human cells to discuss the future direction of the three types of human iPSC-derived cells.

scholarly journals Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases

2021 ◽  
Vol 22 (15) ◽  
pp. 8196
Author(s):  
Dorit Trudler ◽  
Swagata Ghatak ◽  
Stuart A. Lipton
Keyword(s):  
Drug Discovery ◽  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Neural Function ◽  
Neural Cells ◽  
Human Samples ◽  
Healthy Donors ◽  
Induced Pluripotent

Neurodegenerative diseases affect millions of people worldwide and are characterized by the chronic and progressive deterioration of neural function. Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), represent a huge social and economic burden due to increasing prevalence in our aging society, severity of symptoms, and lack of effective disease-modifying therapies. This lack of effective treatments is partly due to a lack of reliable models. Modeling neurodegenerative diseases is difficult because of poor access to human samples (restricted in general to postmortem tissue) and limited knowledge of disease mechanisms in a human context. Animal models play an instrumental role in understanding these diseases but fail to comprehensively represent the full extent of disease due to critical differences between humans and other mammals. The advent of human-induced pluripotent stem cell (hiPSC) technology presents an advantageous system that complements animal models of neurodegenerative diseases. Coupled with advances in gene-editing technologies, hiPSC-derived neural cells from patients and healthy donors now allow disease modeling using human samples that can be used for drug discovery.

Sign in / Sign up

Export Citation Format

Share Document