Current progress in understanding schizophrenia using genomics and pluripotent stem cells: A meta-analytical overview

Choudhary, Ashwani; Peles, David; Nayak, Ritu; Mizrahi, Liron; Stern, Shani

doi:10.1016/j.schres.2022.11.001

“…Its components are, however, poorly regulated in disease, and as a result, myriad of ECM changes occur during pathogenesis (2,11,14). Over the past few decades, the application of high-throughput technologies have fundamentally advanced our understanding of disease mechanisms (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). However, understanding the link between neurons and the surrounding ECM still remains a formidable task (11).…”

Section: Introductionmentioning

confidence: 99%

Proteins and transcriptional dysregulation of the brain extracellular matrix in Parkinson’s disease: A systematic review

Rike

¹

,

Stern

²

2023

Preprint

Self Cite

View full text Add to dashboard Cite

The extracellular matrix (ECM) of the brain is a dynamic structure made up of a vast network of bioactive macromolecules that modulate cellular events. Structural, organizational and functional changes in these macromolecules due to genetic variation or environmental stressors are thought to affect the cellular functions, and may result in disease. Most mechanistic studies to date usually focus on the cellular aspects of diseases and pay less attention to the relevance of the processes governing the dynamic nature of the extracellular matrix on disease pathogenesis. Here in this review, we gathered postmortem brain tissue and induced pluripotent stem cell (iPSC)-related studies from PubMed and Google scholar to identify, summarize and describe common macromolecular alterations in the expression of brain ECM components in Parkinson’s disease (PD). According to proteomic studies, proteins such as collagens, fibronectin, annexins and tenascins were recognized to be differentially expressed in Parkinson’s disease. Transcriptomic studies displayed dysregulated pathways including ECM-receptor interaction, focal adhesion, and cell adhesion molecules in Parkinson’s disease. Limited number of relevant studies were accessed from our search indicating that much work still remains to be done to better understand the roles of the ECM in neurodegeneration and Parkinson’s disease. However, we believe that our review will elicit focused primary studies and thus, support the ongoing efforts of the discovery and development of diagnostic biomarkers as well as therapeutic agents for Parkinson’s disease.

show abstract

“…iPSC-based models offer an alternative to understanding the effect of genomic mutations and associations on neural cells 6,16,21,[43][44][45][46][47][48] . The majority of studies investigated NPCs and neurons derived from ASD patient-specific iPSC in vitro and only a few havestudied the role of glial cells from ASD patients using iPSC technology.…”

Section: Discussionmentioning

confidence: 99%

“…The genetic variant analysis and the standardization of gene nomenclature were performed according to Choudhary et al, 2022 6 . Trait statistics were retrieved from the NHGRI-EBI Genome-Wide Association Study (GWAS) Catalog 27 for the study of ASD (EFO_0003756) and SCZ (EFO_0004609).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Uncovering convergence and divergence between autism and schizophrenia using genomic tools and patients’ neurons

Romanovsky,

Choudhary,

Peles

et al. 2023

Preprint

Self Cite

3

0

View full text Add to dashboard Cite

Autism spectrum disorders (ASDs) are a highly heritable and complex group of psychiatric conditions resulting in abnormal repetitive behaviors and impairment in communication and cognitive skills in children. Recent efforts have led to unmasking some of the genetic and environmental risk factors that contribute to the manifestation of ASD. Previous studies have focused on the genetic correlation between ASDs and other neuropsychiatric disorders but an in-depth understanding of the common variants and its correlation to other disorders is required. In this study, we have conducted an extensive analysis of the common variants identified in ASDs by Genome-wide association studies (GWAS) and compared it to the consensus genes and single nucleotide polymorphisms (SNPs) of Schizophrenia (SCZ) that we have recently reported to determine the shared genetic associations in both the disorders. Further, using a meta-analytical approach we have also probed the cellular phenotypes observed in ASD and compared it to the phenotypes observed in SCZ induced pluripotent stem cell (iPSC) models. Our collective analysis of the deficits in ASD in comparison to SCZ iPSC-derived neurons indicates the presence of developmental divergent trajectories of neuronal pathophysiology that converge to similar phenotypes after the neuronal cells have matured even though the disorders share a high percentage of genetic mutations.

show abstract

“…Over the past few decades, the application of high-throughput technologies has fundamentally advanced our understanding of disease mechanisms [ 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. However, understanding the link between cells and the surrounding ECM remains a formidable task [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Proteins and Transcriptional Dysregulation of the Brain Extracellular Matrix in Parkinson’s Disease: A Systematic Review

Rike

¹

,

Stern

²

2023

IJMS

View full text Add to dashboard Cite

The extracellular matrix (ECM) of the brain is a dynamic structure made up of a vast network of bioactive macromolecules that modulate cellular events. Structural, organizational, and functional changes in these macromolecules due to genetic variation or environmental stressors are thought to affect cellular functions and may result in disease. However, most mechanistic studies to date usually focus on the cellular aspects of diseases and pay less attention to the relevance of the processes governing the dynamic nature of the extracellular matrix in disease pathogenesis. Thus, due to the ECM’s diversified biological roles, increasing interest in its involvement in disease, and the lack of sufficient compiled evidence regarding its relationship with Parkinson’s disease (PD) pathology, we aimed to compile the existing evidence to boost the current knowledge on the area and provide refined guidance for the future research. Here, in this review, we gathered postmortem brain tissue and induced pluripotent stem cell (iPSC)-related studies from PubMed and Google Scholar to identify, summarize and describe common macromolecular alterations in the expression of brain ECM components in Parkinson’s disease (PD). A literature search was conducted up until 10 February 2023. The overall hits from the database and manual search for proteomic and transcriptome studies were 1243 and 1041 articles, respectively. Following a full-text review, 10 articles from proteomic and 24 from transcriptomic studies were found to be eligible for inclusion. According to proteomic studies, proteins such as collagens, fibronectin, annexins, and tenascins were recognized to be differentially expressed in Parkinson’s disease. Transcriptomic studies displayed dysregulated pathways including ECM–receptor interaction, focal adhesion, and cell adhesion molecules in Parkinson’s disease. A limited number of relevant studies were accessed from our search, indicating that much work remains to be carried out to better understand the roles of the ECM in neurodegeneration and Parkinson’s disease. However, we believe that our review will elicit focused primary studies and thus support the ongoing efforts of the discovery and development of diagnostic biomarkers as well as therapeutic agents for Parkinson’s disease.

show abstract

Current progress in understanding schizophrenia using genomics and pluripotent stem cells: A meta-analytical overview

Cited by 15 publications

References 114 publications

Proteins and transcriptional dysregulation of the brain extracellular matrix in Parkinson’s disease: A systematic review

Proteins and transcriptional dysregulation of the brain extracellular matrix in Parkinson’s disease: A systematic review

Uncovering convergence and divergence between autism and schizophrenia using genomic tools and patients’ neurons

Proteins and Transcriptional Dysregulation of the Brain Extracellular Matrix in Parkinson’s Disease: A Systematic Review

Contact Info

Product

Resources

About