Biology subjects

Namipashaki, A.

Publications and source records attributed to Namipashaki, A..

4 recordsLinked to original sources

bioRxiv2026

A neuroimmune IL-13 axis is associated with human enteric nervous system development

The mechanisms governing maturation of the human enteric nervous system (ENS) during early postnatal life remain poorly defined. Here, we characterize the transcriptomic, cellular, and functional landscape of the neonatal human ileum and identify a neuro-immune axis associated with ENS expansion. Using human tissue transcriptomics, flow cytometry, iPSC-derived enteric neural lineages, and single-cell interactome analyses, we show that the neonatal ileum is enriched for pro-neurogenic transcriptional programs and harbors a greater abundance of enteric neurons and glia than the adult tissue. T cells emerge as a predominant source of interleukin-13 (IL-13) in the neonatal gut, and enteric neurons express its receptor IL13RA1, enabling direct immune-to-neuron signaling. Functional experiments demonstrate that IL-13 enhances expression of key enteric neuronal markers in a concentration-dependent manner. In parallel, single-cell analyses identify enteric neurons as a major predicted source of macrophage migration inhibitory factor (MIF), with signaling directed toward T and NK cell populations, suggesting that the ENS actively shapes the immune environment it depends upon. Together, these findings support a model in which bidirectional neuro-immune communication establishes a pro-neurogenic niche during a critical window of ENS development. This work positions the neonatal immune system as an active contributor to ENS maturation and offers a new perspective on how neuro-immune crosstalk shapes intestinal development in early life.

neuroscience↗

bioRxiv2024

Mapping the impact of DUSP6 in an ADHD iPSC derived-dopaminergic neuronal model

Although the gene DUSP6 has been implicated as a risk gene for attention deficit hyperactivity disorder (ADHD) in recent GWAS studies, its functional role in the aetiology of the condition remains poorly understood. DUSP6 is reported to regulate dopaminergic neurotransmission by decreasing available synaptic dopamine, suggesting a potential mechanism by which DUSP6 may confer risk to ADHD. In this study, we employed CRISPR-Cas9 to generate isogenic iPSC lines from an individual with ADHD, including heterozygous and homozygous DUSP6 knockouts alongside the parental control. These iPSC lines were differentiated into dopaminergic neurons and assessed at both cellular, and transcriptomic levels. We observed significant increase in extracellular dopamine in proportion to DUSP6 gene dosage, with greater elevation in homozygous compared to heterozygous knockouts. RNA sequencing further supported this finding, showing that DUSP6-knockout increased expression of genes regulating dopamine secretion and synaptic processes critical for dopaminergic system. Beyond dopamine signalling, transcriptomic changes implicated DUSP6 in neurodevelopmental biological mechanisms, essential to the development of ADHD. Furthermore, we identified significant overlaps between DUSP6-regulated genes and those associated with major depression, bipolar disorder, and schizophrenia, suggesting shared genetic pathways potentially influenced by DUSP6. This study provides mechanistic insights into the role that DUSP6 could potentially play in the aetiology of ADHD and its broader implications across related neuropsychiatric conditions.

neuroscience↗

bioRxiv2024

Transcriptome profiling of dopaminergic neurons derived from an ADHD induced pluripotent stem cell (iPSC) model

The most recent ADHD-GWAS meta-analysis highlighted the potential role of 76 genes enriched among genes expressed in early brain development and associated with midbrain dopaminergic neurons. However, the precise functional importance of the GWAS-identified single nucleotide polymorphisms (SNPs) remain unknown. In contrast to GWAS, transcriptome analysis directly investigates gene products by assessing the transcribed RNA. This allows one to gain functional insights into gene expression paving the way for a better understanding of the molecular risk mechanisms of conditions, such as ADHD. In this study, we performed transcriptome profiling of highly homogeneous dopamine neurons developed from induced pluripotent cells (iPSCs) that were derived from an individual with ADHD and a neurotypical comparison individual. Comparative gene expression analysis between the examined lines revealed that the top differentially expressed genes (DEGs) were predominantly associated with nervous system functions related to neuronal development and dopaminergic regulation. Notably, 29 of the DEGs overlapped with those identified by ADHD-GWAS meta- analysis. These genes are overrepresented in biological processes including developmental growth regulation, axonogenesis, and nervous system development. In addition, gene set analysis revealed significant enrichment for meta categories such as ion channel activity, synaptic function and assembly, neuronal development and cell differentiation. Further, we observed significantly reduced projections in the ADHD dopamine neurons at the mid- differentiation stage (day 14 in vitro), providing preliminary support for the delayed neuronal maturation hypotheses of ADHD. This study underscores the potential of using iPSC-derived cell type-specific models that integrate genome and transcriptome analyses for biological discovery in ADHD.

neuroscience↗

bioRxiv2022

An Efficient CRISPR-Cas9 DNA Editing Methodology Applicable for iPSC Disease Modelling

The capability to generate induced pluripotent stem cell (iPSC) lines, in tandem with CRISPR-Cas9 DNA editing, offers great promise to understand the underlying genetic mechanisms of human disease. The low efficiency of available methods for homogeneous expansion of singularised CRISPR-transfected iPSCs necessitates the coculture of transfected cells in mixed populations and/or on feeder layers. Consequently, edited cells must be purified using labour-intensive screening and selection, culminating in inefficient editing. Here, we provide a xeno-free method for single-cell cloning of CRISPRed iPSCs achieving a clonal survival of up to 70% within 7-10 days. This was accomplished through improved viability of the transfected cells, paralleled with provision of enriched environment for the robust establishment and proliferation of singularised iPSC clones. Enhanced cell survival was accompanied by a high transfection efficiency exceeding 97%, and editing efficiencies of 50-65% for NHEJ and 10% for HDR, indicative of the methods utility in stem cell disease modelling.

genetics↗