Generation of induced pluripotent stem cells from a patient with X-linked juvenile retinoschisis

Peng, Chi Hsien; Huang, Kang-Chieh; Lu, Huai En; Syu, Shih Han; Yarmishyn, Aliaksandr A.; Lu, Jyh-Feng; Buddhakosai, Waradee; Lin, Tzu‐Chin; Hsu, Chih Chien; Hwang, De‐Kuang; Shen, Chia‐Ning; Chen, Shih‐Jen; Chiou, Shih Hwa

doi:10.1016/j.scr.2018.04.005

Cited by 5 publications

(3 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At least two independent hiPSC clonal lines were generated from each XLRS patient or control donor, and all control-donor- and patient-derived hiPSC clones exhibited normal karyotypes and expressed human PSC markers (Figures S2A–S2C). Genotyping of the XLRS patient-derived hiPSC clones confirmed the presence of the respective RS1 mutations at c.625C>T and c.488G>A (Figure 1B) (Peng et al., 2018). We then applied a stepwise three-dimensional (3D) retinal organoid formation protocol (Figure 1C) (Ohlemacher et al., 2015, Zhong et al., 2014) on the hiPSCs of control donors (Ctrl-1 and Ctrl-2) and XLRS patients (Pt-1 and Pt-2) to generate 3D retinal organoids.…”

Section: Resultsmentioning

confidence: 92%

Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

et al. 2019

Self Cite

View full text Add to dashboard Cite

SummaryX-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal organoid in vitro differentiation system. This model recapitulates key features of XLRS including retinal splitting, defective retinoschisin production, outer-segment defects, abnormal paxillin turnover, and impaired ER-Golgi transportation. RS1 mutation also affects the development of photoreceptor sensory cilia and results in altered expression of other retinopathy-associated genes. CRISPR/Cas9 correction of the disease-associated C625T mutation normalizes the splitting phenotype, outer-segment defects, paxillin dynamics, ciliary marker expression, and transcriptome profiles. Likewise, mutating RS1 in control hiPSCs produces the disease-associated phenotypes. Finally, we show that the C625T mutation can be repaired precisely and efficiently using a base-editing approach. Taken together, our data establish 3D organoids as a valid disease model.

show abstract

Section: Resultsmentioning

confidence: 92%

Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…The studies of optic neuropathies caused by genetic determinants using hPSCs are of particular interest as they are the result of known mutations, which allow for a more direct connection of cellular changes to a particular phenotype [5,7]. Patient-specific hPSCs can be differentiated into retinal cell types such as photoreceptors and RPE in a consistent and reproducible manner to study retinal degenerative disorders that cause damage to more outer retinal cell types, with the remarkable ability to use such cells for drug screening, cell replacement, and targeted therapeutics [11,12,[20][21][22][23][24][25][26][27]. Such studies have conducted thorough and in-depth experiments that have identified specific cellular changes in outer retinal cell types such as oxidative and ER stress, autophagy deficits, alterations in protein trafficking, and phagocytotic defects associated with disease-causing mutations.…”

Section: Applications Of Hpscsmentioning

confidence: 99%

Advances in the Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells

Ohlemacher

Langer

Fligor

et al. 2019

Pluripotent Stem Cells in Eye Disease Therapy

View full text Add to dashboard Cite

Human pluripotent stem cell (hPSC) technology has revolutionized the field of biology through the unprecedented ability to study the differentiation of human cells in vitro. In the past decade, hPSCs have been applied to study development, model disease, develop drugs, and devise cell replacement therapies for numerous biological systems. Of particular interest is the application of this technology to study and treat optic neuropathies such as glaucoma. Retinal ganglion cells (RGCs) are the primary cell type affected in these diseases, and once lost, they are unable to regenerate in adulthood. This necessitates the development of strategies to study the mechanisms of degeneration as well as develop translational therapeutic approaches to treat early-and latestage disease progression. Numerous protocols have been established to derive RGCs from hPSCs, with the ability to generate large populations of human RGCs for translational applications. In this review, the key applications of hPSCs within the retinal field are described, including the use of these cells as developmental models, disease models, drug development, and finally, cell replacement therapies. In greater detail, the current report focuses on the differentiation of hPSCderived RGCs and the many unique characteristics associated with these cells in vitro including

show abstract

“…Induced pluripotent stem cell (iPSC) technologies have been shown to hold great promise for personalized therapy, translation medicine, and regeneration medicine [1]. Owing to the potential of iPSCs to be generated from somatic cells via the transduction of specific transcription factors [2], scientists reprogrammed patient-derived somatic cells to generate patient-specific iPSCs [3][4][5]. Remarkably, silencing the expression of human leukocyte antigen (HLA) class I allows to establish the universal human leukocyte antigen 2 of 18 (HLA) iPSCs characterized by low immunogenicity [6].…”

Section: Introductionmentioning

confidence: 99%

Recognizing the Differentiation Degree of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cells Using Machine Learning and Deep Learning-Based Approaches

Lien

Chen

Tsai

et al. 2023

Cells

Self Cite

View full text Add to dashboard Cite

Induced pluripotent stem cells (iPSCs) can be differentiated into mesenchymal stem cells (iPSC-MSCs), retinal ganglion cells (iPSC-RGCs), and retinal pigmental epithelium cells (iPSC-RPEs) to meet the demand of regeneration medicine. Since the production of iPSCs and iPSC-derived cell lineages generally requires massive and time-consuming laboratory work, artificial intelligence (AI)-assisted approach that can facilitate the cell classification and recognize the cell differentiation degree is of critical demand. In this study, we propose the multi-slice tensor model, a modified convolutional neural network (CNN) designed to classify iPSC-derived cells and evaluate the differentiation efficiency of iPSC-RPEs. We removed the fully connected layers and projected the features using principle component analysis (PCA), and subsequently classified iPSC-RPEs according to various differentiation degree. With the assistance of the support vector machine (SVM), this model further showed capabilities to classify iPSCs, iPSC-MSCs, iPSC-RPEs, and iPSC-RGCs with an accuracy of 97.8%. In addition, the proposed model accurately recognized the differentiation of iPSC-RPEs and showed the potential to identify the candidate cells with ideal features and simultaneously exclude cells with immature/abnormal phenotypes. This rapid screening/classification system may facilitate the translation of iPSC-based technologies into clinical uses, such as cell transplantation therapy.

show abstract

Generation of induced pluripotent stem cells from a patient with X-linked juvenile retinoschisis

Cited by 5 publications

References 3 publications

Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

Advances in the Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells

Recognizing the Differentiation Degree of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cells Using Machine Learning and Deep Learning-Based Approaches

Contact Info

Product

Resources

About