scholarly journals Generation of a Panel of Induced Pluripotent Stem Cells From Chimpanzees: a Resource for Comparative Functional Genomics

2014 ◽  
Author(s):  
Irene Gallego Romero ◽  
Bryan J Pavlovic ◽  
Irene Hernando-Herraez ◽  
Nicholas E Banovich ◽  
Courtney L Kagan ◽  
...  
Keyword(s):  
Somatic Cells ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Model Systems ◽  
Sequencing Data ◽  
Differentiation Potential ◽  
Culture Techniques ◽  
Human Ipscs ◽  
Wide Range ◽  
Induced Pluripotent

Comparative genomics studies in primates are extremely restricted because we only have access to a few types of cell lines from non-human apes and to a limited collection of frozen tissues. In order to gain better insight into regulatory processes that underlie variation in complex phenotypes, we must have access to faithful model systems for a wide range of tissues and cell types. To facilitate this, we have generated a panel of 7 fully characterized chimpanzee (Pan troglodytes) induced pluripotent stem cell (iPSC) lines derived from fibroblasts of healthy donors. All lines appear to be free of integration from exogenous reprogramming vectors, can be maintained using standard iPSC culture techniques, and have proliferative and differentiation potential similar to human and mouse lines. To begin demonstrating the utility of comparative iPSC panels, we collected RNA sequencing data and methylation profiles from the chimpanzee iPSCs and their corresponding fibroblast precursors, as well as from 7 human iPSCs and their precursors, which were of multiple cell type and population origins. Overall, we observed much less regulatory variation within species in the iPSCs than in the somatic precursors, indicating that the reprogramming process has erased many of the differences observed between somatic cells of different origins. We identified 4,918 differentially expressed genes and 3,598 differentially methylated regions between iPSCs of the two species, many of which are novel inter-species differences that were not observed between the somatic cells of the two species. Our panel will help realise the potential of iPSCs in primate studies, and in combination with genomic technologies, transform studies of comparative evolution.

scholarly journals A panel of induced pluripotent stem cells from chimpanzees: a resource for comparative functional genomics

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Irene Gallego Romero ◽  
Bryan J Pavlovic ◽  
Irene Hernando-Herraez ◽  
Xiang Zhou ◽  
Michelle C Ward ◽  
...  
Keyword(s):  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Model Systems ◽  
Species Variation ◽  
Small Magnitude ◽  
Healthy Donors ◽  
Human Ipscs ◽  
Wide Range ◽  
Induced Pluripotent ◽  
Comparative Functional Genomics

Comparative genomics studies in primates are restricted due to our limited access to samples. In order to gain better insight into the genetic processes that underlie variation in complex phenotypes in primates, we must have access to faithful model systems for a wide range of cell types. To facilitate this, we generated a panel of 7 fully characterized chimpanzee induced pluripotent stem cell (iPSC) lines derived from healthy donors. To demonstrate the utility of comparative iPSC panels, we collected RNA-sequencing and DNA methylation data from the chimpanzee iPSCs and the corresponding fibroblast lines, as well as from 7 human iPSCs and their source lines, which encompass multiple populations and cell types. We observe much less within-species variation in iPSCs than in somatic cells, indicating the reprogramming process erases many inter-individual differences. The low within-species regulatory variation in iPSCs allowed us to identify many novel inter-species regulatory differences of small magnitude.

scholarly journals CellMap: Characterizing the types and composition of iPSC-derived cells from RNA-seq data

2021 ◽  
Author(s):  
Zhengyu Ouyang ◽  
Nathanael Bourgeois ◽  
Eugenia Lyashenko ◽  
Paige Cundiff ◽  
Patrick F Cullen ◽  
...  
Keyword(s):  
Single Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Model Systems ◽  
Rna Seq ◽  
Cell Type ◽  
Fine Grained ◽  
Single Nucleus ◽  
Induced Pluripotent

Induced pluripotent stem cell (iPSC) derived cell types are increasingly employed as in vitro model systems for drug discovery. For these studies to be meaningful, it is important to understand the reproducibility of the iPSC-derived cultures and their similarity to equivalent endogenous cell types. Single-cell and single-nucleus RNA sequencing (RNA-seq) are useful to gain such understanding, but they are expensive and time consuming, while bulk RNA-seq data can be generated quicker and at lower cost. In silico cell type decomposition is an efficient, inexpensive, and convenient alternative that can leverage bulk RNA-seq to derive more fine-grained information about these cultures. We developed CellMap, a computational tool that derives cell type profiles from publicly available single-cell and single-nucleus datasets to infer cell types in bulk RNA-seq data from iPSC-derived cell lines.

scholarly journals Present and future challenges of induced pluripotent stem cells

2015 ◽  
Vol 370 (1680) ◽  
pp. 20140367 ◽  
Author(s):  
Mari Ohnuki ◽  
Kazutoshi Takahashi
Keyword(s):  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Disease Modelling ◽  
Future Perspectives ◽  
Differentiated Cells ◽  
Human Ipscs ◽  
Future Challenges ◽  
Induced Pluripotent

Growing old is our destiny. However, the mature differentiated cells making up our body can be rejuvenated to an embryo-like fate called pluripotency which is an ability to differentiate into all cell types by enforced expression of defined transcription factors. The discovery of this induced pluripotent stem cell (iPSC) technology has opened up unprecedented opportunities in regenerative medicine, disease modelling and drug discovery. In this review, we introduce the applications and future perspectives of human iPSCs and we also show how iPSC technology has evolved along the way.

scholarly journals Engineered human induced pluripotent cells enable genetic code expansion in brain organoids

2021 ◽  
Author(s):  
Lea van Husen ◽  
Anna Maria Katsori ◽  
Birthe Meineke ◽  
Lars O Tjernberg ◽  
Sophia Schedin-Weiss ◽  
...  
Keyword(s):  
Genetic Code ◽  
Fluorescent Dyes ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Trna Synthetase ◽  
Induced Pluripotent Cells ◽  
Wide Range ◽  
Induced Pluripotent ◽  
Human Induced Pluripotent Cells ◽  
Tissue Models

Human induced pluripotent stem cell (hiPSC) technology has revolutionized human biology. A wide range of cell types and tissue models can be derived from hiPSCs to study complex human diseases. Here, we use PiggyBac mediated transgenesis to engineer hiPSCs with an expanded genetic code. We demonstrate that genomic integration of expression cassettes for a pyrrolysyl-tRNA synthetase (PylRS), pyrrolysyl-tRNA (PylT) and the target protein of interest enables site-specific incorporation of a non-canonical amino acid (ncAA) in response to amber stop codons. Neural stem cells, neurons and brain organoids derived from the engineered hiPSCs continue to express the amber suppression machinery and produce ncAA-bearing reporter. The incorporated ncAA can serve as a minimal bioorthogonal handle for further modifications by labeling with fluorescent dyes. Site-directed ncAA mutagenesis will open a wide range of applications to probe and manipulate proteins in brain organoids and other hiPSC-derived cell types and complex tissue models.

scholarly journals The utilisation of organoids and macrophages derived from Human induced pluripotent stem cells as model systems to investigate host-bacterial interactions

2019 ◽  
Vol 1 (1A) ◽  
Author(s):  
Christine Hale ◽  
Leanne Kane ◽  
Matthew Dorman ◽  
Nicholas Thomson
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Genetically Engineered ◽  
Model Systems ◽  
Host Cells ◽  
Bacterial Interactions ◽  
Induced Pluripotent

Using human induced pluripotent stem cell (hiPSC) technology we are developing methods to examine host-bacterial interactions. Due to the fact that undifferentiated human induced pluripotent stem cells are amenable to genetic engineering, can be cultured indefinitely and can further be differentiated into multiple cell types, we are exploiting both organoid and macrophage systems to investigate the interactions between host cells and diarrhoeal pathogens, including enterotoxigenic Escherichia coli and Vibrio cholerae. Utilising both wild type and relevant knockout hiPSC lines we are probing both initial interactions and subsequent utilisation of pathways for the effects of toxins. The further analysis of genetically engineered bacteria extend the usefulness of this model system, and complement the availability of mutant host cells, towards the simultaneous genetic analysis of both pathogen and host.

Abstract 17784: The Genesips Project: an NHLBI-Sponsored induced Pluripotent Stem Cell (iPSC) Resource for the Study of Cardiovascular Diseases

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ivan Carcamo-Orive ◽  
Paige Cundiff ◽  
Hope Lancero ◽  
Mohammad Shahbazi ◽  
Fahim Abbasi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Sendai Virus ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Model Systems ◽  
Molecular Pathways ◽  
Induced Pluripotent

The study of complex cardiovascular disease (CVD) has been hampered by the lack of appropriate human cellular model systems. In response, the NHBLI sponsored the NextGen Consortium, which encompasses 9 independent efforts spanning the portfolio of NHLBI related phenotypes. The goals of the consortium include: 1. To develop and improve methods for large-scale production and characterization of induced pluripotent stem cell (iPSC) models for CVD; 2. To create a resource of iPSC lines from a large number of phenotypically and genotypically characterized individuals. Our GENESiPS project is focused on insulin resistance (IR), a condition that affects 25-33% of the US population with serious health consequences including risk of type II diabetes and CVD. Although much is known about the physiological changes occurring during IR, little is known about the molecular pathways that drive the appearance of IR. Certain mature cell types as adipocytes, endothelial cells and skeletal muscle cells have been associated with the origin, maintenance and progression of IR. IPSCs offer an unprecedented opportunity of modeling human disease in vitro. We have created iPSC lines on insulin resistant and insulin sensitive patient groups with prior GWAS genotyping. Differentiation of these iPSCs to relevant cell types is providing the opportunity to correlate insulin sensitivity and high-density genetic variation data with specific cell-based profiling. We will validate our in vitro model and study the molecular pathways that define IR and its relationship to endothelial dysfunction. Relevant to the larger scientific community the establishment of iPSC lines on over 150 individuals (3 to 6 clones per patient) that reflect the range of insulin resistance in the general population. The iPSC lines were created from erythroblasts using the non-integrative Sendai virus system, passaged to allow clearance of Sendai virus and growth in feeder free conditions. The lines have been extensively characterized for markers of pluripotency (Tra1-60), sample identity and genomic integrity. Through the NextGen consortium, these lines, as well as phenotypic and genome-wide genotyping data will be available to qualified investigators.

scholarly journals Human Induced Pluripotent Stem Cells Derived from a Cardiac Somatic Source: Insights for an In-Vitro Cardiomyocyte Platform

2020 ◽  
Vol 21 (2) ◽  
pp. 507
Author(s):  
Alessandra Maria Lodrini ◽  
Lucio Barile ◽  
Marcella Rocchetti ◽  
Claudia Altomare
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Cardiac Cells ◽  
Cardiac Differentiation ◽  
Human Ipscs ◽  
Wide Range ◽  
Induced Pluripotent

Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) has revolutionized the complex scientific field of disease modelling and personalized therapy. Cardiac differentiation of human iPSCs into cardiomyocytes (hiPSC-CMs) has been used in a wide range of healthy and disease models by deriving CMs from different somatic cells. Unfortunately, hiPSC-CMs have to be improved because existing protocols are not completely able to obtain mature CMs recapitulating physiological properties of human adult cardiac cells. Therefore, improvements and advances able to standardize differentiation conditions are needed. Lately, evidences of an epigenetic memory retained by the somatic cells used for deriving hiPSC-CMs has led to evaluation of different somatic sources in order to obtain more mature hiPSC-derived CMs.

scholarly journals Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia

2021 ◽  
Vol 22 (9) ◽  
pp. 4334
Author(s):  
Katrina Albert ◽  
Jonna Niskanen ◽  
Sara Kälvälä ◽  
Šárka Lehtonen
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Induced Pluripotent Stem Cells ◽  
Glial Cells ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Human Ipscs ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) are a self-renewable pool of cells derived from an organism’s somatic cells. These can then be programmed to other cell types, including neurons. Use of iPSCs in research has been two-fold as they have been used for human disease modelling as well as for the possibility to generate new therapies. Particularly in complex human diseases, such as neurodegenerative diseases, iPSCs can give advantages over traditional animal models in that they more accurately represent the human genome. Additionally, patient-derived cells can be modified using gene editing technology and further transplanted to the brain. Glial cells have recently become important avenues of research in the field of neurodegenerative diseases, for example, in Alzheimer’s disease and Parkinson’s disease. This review focuses on using glial cells (astrocytes, microglia, and oligodendrocytes) derived from human iPSCs in order to give a better understanding of how these cells contribute to neurodegenerative disease pathology. Using glia iPSCs in in vitro cell culture, cerebral organoids, and intracranial transplantation may give us future insight into both more accurate models and disease-modifying therapies.

scholarly journals A non-invasive method to generate induced pluripotent stem cells from primate urine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Johanna Geuder ◽  
Lucas E. Wange ◽  
Aleksandar Janjic ◽  
Jessica Radmer ◽  
Philipp Janssen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Sendai Virus ◽  
Cell Types ◽  
Urine Samples ◽  
Comparative Approach ◽  
Non Invasive ◽  
Human Ipscs ◽  
Induced Pluripotent

AbstractComparing the molecular and cellular properties among primates is crucial to better understand human evolution and biology. However, it is difficult or ethically impossible to collect matched tissues from many primates, especially during development. An alternative is to model different cell types and their development using induced pluripotent stem cells (iPSCs). These can be generated from many tissue sources, but non-invasive sampling would decisively broaden the spectrum of non-human primates that can be investigated. Here, we report the generation of primate iPSCs from urine samples. We first validate and optimize the procedure using human urine samples and show that suspension- Sendai Virus transduction of reprogramming factors into urinary cells efficiently generates integration-free iPSCs, which maintain their pluripotency under feeder-free culture conditions. We demonstrate that this method is also applicable to gorilla and orangutan urinary cells isolated from a non-sterile zoo floor. We characterize the urinary cells, iPSCs and derived neural progenitor cells using karyotyping, immunohistochemistry, differentiation assays and RNA-sequencing. We show that the urine-derived human iPSCs are indistinguishable from well characterized PBMC-derived human iPSCs and that the gorilla and orangutan iPSCs are well comparable to the human iPSCs. In summary, this study introduces a novel and efficient approach to non-invasively generate iPSCs from primate urine. This will extend the zoo of species available for a comparative approach to molecular and cellular phenotypes.

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