Generation of transgene-free iPSC lines from three patients with Friedreich’s ataxia (FRDA) carrying GAA triplet expansions in the first intron of FXN gene

Kelekçi, Simge; Uğurlu-Çimen, Deniz; Ata, Demir Berk; Özçimen, Burcu; Yıldız, Abdullah Burak; Karakuş, Mehmet Batuhan; Yücel, Esra Börklü; Önder, Tamer T.

doi:10.1016/j.scr.2021.102438

Cited by 2 publications

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“…FXN downregulation observed in fibroblasts was found to be retained in the iPSCs ( Ku et al, 2010 ). Since then, several additional FRDA patient-derived iPSCs were generated to study the pathophysiology of this disease ( Liu et al, 2011 ; Bolotta et al, 2019 ; Schreiber et al, 2019 ; Dionisi et al, 2020 ; Mazzara et al, 2020 ; Angulo et al, 2021 ; Kelekci et al, 2021 ).…”

Section: Generation Of Patient-specific Induced Pluripotent Stem Cellsmentioning

confidence: 99%

“…In vivo models of FRDA include yeast, nematode worm, fruit fly, and mice ( Babcock et al, 1997 ; Radisky et al, 1999 ; Puccio et al, 2001 ; Al-Mahdawi et al, 2004 ; Vázquez-Manrique et al, 2006 ; Virmouni et al, 2014 ; Monnier et al, 2018 ), whereas FRDA in vitro models include patient-derived cells such as immortalized lymphoblastoid cells, primary fibroblasts ( Li et al, 2016 ; Agro and Diaz-Nido, 2020 ; Misiorek et al, 2020 ; Johnson et al, 2021 ), FRDA-derived iPSCs ( Angulo et al, 2021 ; Kelekci et al, 2021 ), and iPSC-based models such as neurons, cardiomyocytes, and beta cells ( Crombie et al, 2016 ; Schreiber et al, 2019 ) ( Figure 1 ). All these FRDA models need to imitate the symptoms of FRDA patients.…”

Section: Introductionmentioning

confidence: 99%

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Perspectives on current models of Friedreich’s ataxia

Kelekçi

Yıldız

Sevinç

et al. 2022

Front. Cell Dev. Biol.

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Friedreich’s ataxia (FRDA, OMIM#229300) is the most common hereditary ataxia, resulting from the reduction of frataxin protein levels due to the expansion of GAA repeats in the first intron of the FXN gene. Why the triplet repeat expansion causes a decrease in Frataxin protein levels is not entirely known. Generation of effective FRDA disease models is crucial for answering questions regarding the pathophysiology of this disease. There have been considerable efforts to generate in vitro and in vivo models of FRDA. In this perspective article, we highlight studies conducted using FRDA animal models, patient-derived materials, and particularly induced pluripotent stem cell (iPSC)-derived models. We discuss the current challenges in using FRDA animal models and patient-derived cells. Additionally, we provide a brief overview of how iPSC-based models of FRDA were used to investigate the main pathways involved in disease progression and to screen for potential therapeutic agents for FRDA. The specific focus of this perspective article is to discuss the outlook and the remaining challenges in the context of FRDA iPSC-based models.

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Section: Generation Of Patient-specific Induced Pluripotent Stem Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Perspectives on current models of Friedreich’s ataxia

Kelekçi

Yıldız

Sevinç

et al. 2022

Front. Cell Dev. Biol.

Self Cite

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Optimized Method for Using Embryonic Microenvironment to Reprogram Cancer Stem Cells

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Oltulu

Çal

et al. 2023

Journal of Basic and Clinical Health Sciences

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Purpose: The embryonic microenvironment contains many properties that have not yet been fully explored. Our aim in this study is to report an optimized and efficient method that enables investigating the effects of the secretome of pluripotent embryonic stem cells on cancer stem cells. Methods: The study is performed with a chimeric model consisted of mouse blastocysts, human prostate cancer stem cells and non-cancer stem cells. Ovulation induced mice were used for blastocyst collection. DU145 prostate cancer cell line was separated into cancer stem cells and non-cancer stem cells according to cancer stem cells biomarker expressions by fluorescent activated cell sorting method. Human prostate cancer stem cells and non-cancer stem cells were microinjected into 4-day blastocyst culture in vitro by intracytoplasmic sperm injection method. Results: Chimeric models provide us great convenience in basic oncological studies. In this study, using a chimeric model, we were able to study the secretome of mouse embryonic stem cells and their effect on cancer stem cells. The method is efficient and yield promising result; and could be used to study the effects on other cells as well. Conclusion: The embryonic stem cell microenvironment is suggested to have a great regenerative capacity which is, nowadays, the center of attraction for cancer research studies. Ethical issues restrict the human embryo studies, however, mimicking the in vivo human microenvironment with 3D cell cultures or bioprinting are now possible. Finally, optimization of new methods including 3D cell cultures with human cell lines will be a great opportunity for better understanding the reprogramming notion.

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Generation of transgene-free iPSC lines from three patients with Friedreich’s ataxia (FRDA) carrying GAA triplet expansions in the first intron of FXN gene

Cited by 2 publications

References 5 publications

Perspectives on current models of Friedreich’s ataxia

Perspectives on current models of Friedreich’s ataxia

Optimized Method for Using Embryonic Microenvironment to Reprogram Cancer Stem Cells

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