Mouse models and induced pluripotent stem cells in researching psychiatric disorders

Deng, Ben

doi:10.21037/sci.2017.06.10

Cited by 5 publications

(4 citation statements)

References 12 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transcriptional discordance between SLCs derived from hAMSCs versus hiPSCs may in part be attributable to unique cells of origin and the experimental differences related to the reprograming process. While hiPSCs have been utilize successfully to overcome limitations of mouse models to develop to enhance our understanding of psychiatric disorders [42] and Alzheimer's disease [22], further investigation is needed to the validate the fidelity of this platform in recapitulating the pathogenesis of NF2-SWN and other Schwann cell associated disorders. Importantly, despite these differences, our analysis did reveal novel gene signatures associated with Schwann cell development that were conserved across species and model systems.…”

Section: Discussionmentioning

confidence: 99%

A novel induced pluripotent stem cell model of Schwann cell differentiation revealsNF2- related gene regulatory networks of the extracellular matrix

Lazaro,

Li,

Carter

et al. 2024

Preprint

View full text Add to dashboard Cite

Schwann cells are vital to the development and maintenance of the peripheral nervous system and their dysfunction has been implicated in a range of neurological and neoplastic disorders, including NF2-related schwannomatosis. We have developed a novel human induced pluripotent stem cell (hiPSC) model for the study of Schwann cell differentiation in health and disease. We performed transcriptomic, immunofluorescence, and morphological analysis of hiPSC derived Schwann cell precursors (SPCs) and terminally differentiated Schwann-like cells (SLCs) representing distinct stages of development. To further validate our findings, we performed integrated, cross-species analyses across multiple external datasets at bulk and single cell resolution. Our hiPSC model of Schwann cell development shared overlapping gene expression signatures with human amniotic mesenchymal stem cell (hAMSCs) derived SLCs and in vivo mouse models, but also revealed unique features that may reflect species-specific aspects of Schwann cell biology. Moreover, we have identified gene co-expression modules that are dynamically regulated during hiPSC to SLC differentiation associated with ear and neural development, cell fate determination, the NF2 gene, and extracellular matrix (ECM) organization. By cross-referencing results between multiple datasets and analyses, we have identified potential new genes that are related to NF2 for further study including: ANXA1, CDH6, COL1A1, COL8A1, MFAP5, IGFBP5, FGF1, AHNAK, CDKN2B, LOX, CAV1, and CAV2. Our hiPSC model further provides a tractable platform for studying Schwann cell development in the context of human disease.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel induced pluripotent stem cell model of Schwann cell differentiation revealsNF2- related gene regulatory networks of the extracellular matrix

Lazaro,

Li,

Carter

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Although, PROM1 has been previously knocked out in RPE cells [ 30 , 78 ] and murine models [ 79 – 81 ], the application of CRISPR/Cas9 genome editing on patient-derived iPSC to establish IRD-specific disease models enables researchers to study the distinct molecular effects associated with each IRD-related variant, extending beyond the mere absence of a protein as in KO murine models [ 82 , 83 ]. In this regard, the next steps in our research horizon include obtaining gene-edited iPSC-derived RPE cells to evaluate this matter and to future cell therapy assays as they seem to be the most promising alternatives for replacement therapies [ 84 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical exome analysis and targeted gene repair of the c.1354dupT variant in iPSC lines from patients with PROM1-related retinopathies exhibiting diverse phenotypes

Puertas-Neyra,

Coco-Martin,

Hernandez-Rodriguez

et al. 2024

Stem Cell Res Ther

View full text Add to dashboard Cite

Background Inherited retinal dystrophies (IRD) are one of the main causes of incurable blindness worldwide. IRD are caused by mutations in genes that encode essential proteins for the retina, leading to photoreceptor degeneration and loss of visual function. IRD generates an enormous global financial burden due to the lack of understanding of a significant part of its pathophysiology, molecular diagnosis, and the near absence of non-palliative treatment options. Patient-derived induced pluripotent stem cells (iPSC) for IRD seem to be an excellent option for addressing these questions, serving as exceptional tools for in-depth studies of IRD pathophysiology and testing new therapeutic approaches. Methods From a cohort of 8 patients with PROM1-related IRD, we identified 3 patients carrying the same variant (c.1354dupT) but expressing three different IRD phenotypes: Cone and rod dystrophy (CORD), Retinitis pigmentosa (RP), and Stargardt disease type 4 (STGD4). These three target patients, along with one healthy relative from each, underwent comprehensive ophthalmic examinations and their genetic panel study was expanded through clinical exome sequencing (CES). Subsequently, non-integrative patient-derived iPSC were generated and fully characterized. Correction of the c.1354dupT mutation was performed using CRISPR/Cas9, and the genetic restoration of the PROM1 gene was confirmed through flow cytometry and western blotting in the patient-derived iPSC lines. Results CES revealed that 2 target patients with the c.1354dupT mutation presented monoallelic variants in genes associated with the complement system or photoreceptor differentiation and peroxisome biogenesis disorders, respectively. The pluripotency and functionality of the patient-derived iPSC lines were confirmed, and the correction of the target mutation fully restored the capability of encoding Prominin-1 (CD133) in the genetically repaired patient-derived iPSC lines. Conclusions The c.1354dupT mutation in the PROM1 gene is associated to three distinct AR phenotypes of IRD. This pleotropic effect might be related to the influence of monoallelic variants in other genes associated with retinal dystrophies. However, further evidence needs to be provided. Future experiments should include gene-edited patient-derived iPSC due to its potential as disease modelling tools to elucidate this matter in question. Graphical Abstract

show abstract

“…The development of hiPSC-based models represents an interesting alternative to animal models by mimicking steps of human neuronal development [153][154][155]. The generation of hiPSC-derived neurons from Rubinstein Taybi syndrome patients (iNeuron) revealed morphological abnormalities with a reduced size but increased number of neurites and hypoexcitability [156].…”

Section: Chromatinopathies and Neurodevelopmentmentioning

confidence: 99%

Chromatin Structure and Dynamics: Focus on Neuronal Differentiation and Pathological Implication

Nothof

Magdinier

Van-Gils

2022

Genes

View full text Add to dashboard Cite

Chromatin structure is an essential regulator of gene expression. Its state of compaction contributes to the regulation of genetic programs, in particular during differentiation. Epigenetic processes, which include post-translational modifications of histones, DNA methylation and implication of non-coding RNA, are powerful regulators of gene expression. Neurogenesis and neuronal differentiation are spatio-temporally regulated events that allow the formation of the central nervous system components. Here, we review the chromatin structure and post-translational histone modifications associated with neuronal differentiation. Studying the impact of histone modifications on neuronal differentiation improves our understanding of the pathophysiological mechanisms of chromatinopathies and opens up new therapeutic avenues. In addition, we will discuss techniques for the analysis of histone modifications on a genome-wide scale and the pathologies associated with the dysregulation of the epigenetic machinery.

show abstract

Mouse models and induced pluripotent stem cells in researching psychiatric disorders

Cited by 5 publications

References 12 publications

A novel induced pluripotent stem cell model of Schwann cell differentiation revealsNF2- related gene regulatory networks of the extracellular matrix

A novel induced pluripotent stem cell model of Schwann cell differentiation revealsNF2- related gene regulatory networks of the extracellular matrix

Clinical exome analysis and targeted gene repair of the c.1354dupT variant in iPSC lines from patients with PROM1-related retinopathies exhibiting diverse phenotypes

Chromatin Structure and Dynamics: Focus on Neuronal Differentiation and Pathological Implication

Contact Info

Product

Resources

About