Increased Expression of KNa1.2 Channel by MAPK Pathway Regulates Neuronal Activity Following Traumatic Brain Injury

Liu, Ru; Sun, Lei; Shi, Xiaorui; Li, Ci; Guo, Xi; Wang, Yingting; Wang, Xiu; Zhang, Kai; Wang, Yongjun; Wang, Qun; Wu, Jianping

doi:10.1007/s11064-023-04044-1

Cited by 2 publications

(1 citation statement)

References 47 publications

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“…Others have postulated a potential protective role for K Na 1.2 in the acute phase of traumatic brain injury (TBI), based on an increase in K Na 1.2 expression surrounding TBI lesions in the acute phase following TBI in mice with increased neuronal excitability, and seizure susceptibility in KCNT2 -/- mice compared to WT. 47 These results demonstrate that the CaMPARI2 screen is capable of detecting subtle changes to neuronal excitability and can highlight previously under-studied channels for additional characterization.…”

Section: Resultsmentioning

confidence: 70%

A Massively Parallel CRISPR-Based Screening Platform for Modifiers of Neuronal Activity

Boggess,

Gandhi,

Tsai

et al. 2024

Preprint

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Understanding the complex interplay between gene expression and neuronal activity is crucial for unraveling the molecular mechanisms underlying cognitive function and neurological disorders. In this study, we develop pooled screens for neuronal activity, using CRISPR interference (CRISPRi) and the fluorescent calcium integrator CaMPARI2. Using this screening method, we identified 153 genes associated that changed synaptic excitability in human iPSC-derived neurons, revealing potential links to neurodegenerative and neurodevelopmental disorders. These genes include known regulators of neuronal excitability, such as TARPs and ion channels, as well as genes associated with autism spectrum disorder (ASD) and Alzheimer’s disease (AD) not previously described to affect neuronal excitability. This CRISPRi-based screening platform offers a versatile tool to uncover molecular mechanisms controlling neuronal activity in health and disease.

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Section: Resultsmentioning

confidence: 70%

A Massively Parallel CRISPR-Based Screening Platform for Modifiers of Neuronal Activity

Boggess,

Gandhi,

Tsai

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Phenotype Scoring of Population Scale Single-Cell Data Dissects Alzheimer’s Disease Complexity

He,

Li,

Arachchilage

et al. 2024

Preprint

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The complexity of Alzheimer's disease (AD) manifests in diverse clinical phenotypes, including cognitive impairment and neuropsychiatric symptoms (NPSs). However, the etiology of these phenotypes remains elusive. To address this, the PsychAD project generated a population-level single-nucleus RNA-seq dataset comprising over 6 million nuclei from the prefrontal cortex of 1,494 individual brains, covering a variety of AD-related phenotypes that capture cognitive impairment, severity of pathological lesions, and the presence of NPSs. Leveraging this dataset, we developed a deep learning framework, called Phenotype Associated Single Cell encoder (PASCode), to score single-cell phenotype associations, and identified ~1.5 million phenotype associate cells (PACs). We compared PACs within 27 distinct brain cell subclasses and prioritized cell subpopulations and their expressed genes across various AD phenotypes, including the upregulation of a reactive astrocyte subtype with neuroprotective function in AD resilient donors. Additionally, we identified PACs that link multiple phenotypes, including a subpopulation of protoplasmic astrocytes that alter their gene expression and regulation in AD donors with depression. Uncovering the cellular and molecular mechanisms underlying diverse AD phenotypes has the potential to provide valuable insights towards the identification of novel diagnostic markers and therapeutic targets. All identified PACs, along with cell type and gene expression information, are summarized into an AD-phenotypic single-cell atlas for the research community.

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Increased Expression of KNa1.2 Channel by MAPK Pathway Regulates Neuronal Activity Following Traumatic Brain Injury

Cited by 2 publications

References 47 publications

A Massively Parallel CRISPR-Based Screening Platform for Modifiers of Neuronal Activity

A Massively Parallel CRISPR-Based Screening Platform for Modifiers of Neuronal Activity

Phenotype Scoring of Population Scale Single-Cell Data Dissects Alzheimer’s Disease Complexity

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