Biology subjects

Zolfaghar, M.

Publications and source records attributed to Zolfaghar, M..

5 recordsLinked to original sources

bioRxiv2026

Differential Neurodevelopmental Disruption by Bisphenol A (BPA) and Valproic Acid (VPA) in Human Forebrain Organoids

Neurodevelopmental disorders, including autism spectrum disorder (ASD), are influenced by both genetic abnormalities and environmental toxicants. Among environmental risk factors, endocrine-disrupting chemicals such as bisphenol A (BPA) and pharmaceutical drugs such as valproic acid (VPA) have been associated with an increased risk of autism. In this study, human induced pluripotent stem cell (iPSC)-derived forebrain organoids were used to model early neurodevelopmental disruptions induced by BPA and VPA exposure. On day 62 of differentiation, forebrain organoids were treated with physiologically relevant concentrations of BPA or VPA for 28 days. Following treatment, morphological, molecular, and electrophysiological changes were assessed across experimental conditions. Both compounds produced distinct alterations in organoid morphology, neurodevelopmental gene expression, and network electrical activity, with VPA inducing markedly stronger effects. Overall, these data suggest forebrain organoids as a robust, physiologically relevant in vitro model system for studying neurodevelopment. This platform enables systematic investigation of environmental and pharmacological risk factors implicated in the pathogenesis of neurodevelopmental disorders.

neuroscience↗

bioRxiv2024

Cryopreservation of neuroectoderm on a pillar plate and in situ differentiation into human brain organoids

Cryopreservation in cryovials extends cell storage at low temperatures, and advances in organoid cryopreservation improve reproducibility and reduce generation time. However, cryopreserving human organoids presents challenges due to the limited diffusion of cryoprotective agents (CPAs) into the organoid core and the potential toxicity of these agents. To overcome these obstacles, we developed a cryopreservation technique using a pillar plate platform. To illustrate cryopreservation application to human brain organoids (HBOs), early-stage HBOs were produced by differentiating induced pluripotent stem cells (iPSCs) into neuroectoderm (NEs) in an ultralow atachement (ULA) 384-well plate. These NEs were transferred and encapsulated in Matrigel on the pillar plate. The early-stage HBOs on the pillar plate were exposed to four commercially available CPAs, including PSC cryopreservation kit, CryoStor CS10, 3dGRO, and 10% DMSO, before being frozen overnight at -80{degrees}C and subsequently stored in a liquid nitrogen dewar. We examined the impact of CPA type, organoid size, and CPA exposure duration on cell viability post-thaw. Additionally, the differentiation of early-stage HBOs on the pillar plate was assessed using RT-qPCR and immunofluorescence staining. The PSC cryopreservation kit proved to be the least toxic for preserving these HBOs on the pillar plate. Notably, smaller HBOs showed higher cell viability post-cryopreservation than larger ones. An incubation period of 80 minutes with the PSC kit was essential to ensure optimal CPA diffusion into HBOs with a diameter of 400 - 600 {micro}m. These cryopreserved early-stage HBOs successfully matured over 30 days, exhibiting gene expression patterns akin to non-cryopreserved HBOs. The cryopreserved early-stage HBOs on the pillar plate maintained high viability after thawing and successfully differentiated into mature HBOs. This on-chip cryopreservation method could extend to other small organoids, by integrating cryopreservation, thawing, culturing, staining, rinsing, and imaging processes within a single system, thereby preserving the 3D structure of the organoids.

bioengineering↗

bioRxiv2023

A pillar/perfusion plate enhances cell growth, reproducibility, throughput, and user friendliness in dynamic 3D cell culture

Static three-dimensional (3D) cell culture has been demonstrated in ultralow attachment well plates, hanging droplet plates, and microtiter well plates with hydrogels or magnetic nanoparticles. Although it is simple, reproducible, and relatively inexpensive, thus potentially used for high-throughput screening, statically cultured 3D cells often suffer from the necrotic core due to limited nutrient and oxygen diffusion and waste removal and have limited in vivo-like tissue structure. Here, we overcome these challenges by developing a pillar/perfusion plate platform and demonstrating high-throughput, dynamic 3D cell culture. Cell spheroids have been loaded on the pillar plate with hydrogel by simple sandwiching and encapsulation and cultured dynamically in the perfusion plate on a digital rocker. Unlike traditional microfluidic devices, fast flow rates were maintained within perfusion wells, and the pillar plate could be separated from the perfusion plate for cell-based assays. It was compatible with common lab equipment and allowed cell culture, testing, staining, and imaging in situ. The pillar/perfusion plate enhanced cell growth by rapid diffusion, reproducibility, assay throughput, and user friendliness in dynamic 3D cell culture.

bioengineering↗

bioRxiv2023

The representational geometry of cognitive maps under dynamic cognitive control

Recent work has shown that the brain abstracts non-spatial relationships between entities or task states into representations called cognitive maps. Here, we investigate how cognitive control enables flexible top-down selection of goal-relevant information from multidimensional cognitive maps retrieved from memory. We examine the relationship between cognitive control and representational geometry by conducting parallel analyses of functional magnetic resonance imaging data and recurrent neural network models trained to perform the same task. We find both stable map-like representations in a medial temporal lobe and orbitofrontal cortical network that reflect both task-relevant and irrelevant dimensions and context-dependent, orthogonal representations of only task-relevant dimensions in a frontoparietal network. These representational motifs also emerge with distinct temporal profiles over the course of training in the recurrent neural network, with map-like representations appearing first. We further show that increasing control demands due to incongruence (conflicting responses) between current task-relevant and irrelevant dimensions impact the geometry of subjective representations, and the degree of this effect further accounts for individual differences in cognitive control. Taken together, our findings show how complementary representational geometries balance stability and behavioral flexibility, and reveal an intricate relationship between cognitive control and cognitive map geometry.

neuroscience↗

bioRxiv2022

Comparative Transcriptome Analysis of Hypocotyls During the Developmental Transition of C3 cotyledons to C4 Leaves in Halimocnemis mollissima: Exploring Root-Shoot Signalings Involved in the Establishing of C4 traits

Identification of signaling pathways that control C4 photosynthesis development is essential for introducing the C4 pathway into C3 crops. Species with dual photosynthesis in their life cycle are interesting models to study such regulatory mechanisms. The species used here Halimocnemis mollissima Bunge, belonging to the Caroxyleae tribe, displays C3 photosynthesis in its cotyledons and a NAD-ME subtype of C4 photosynthesis in the First leaves (FLs) onwards. We explored the long-distance signaling pathways that are probably implicated in the shoot-root coordination associated with the manifestation of the C4 traits, including efficient resource usage by comparing the mRNA content of hypocotyls before and after the C4 first leaves formation. Histological examination showed the presence of C3 anatomy in cotyledons and C4 anatomy in the FLs. Our transcriptome analyses verified the performance of the NAD-ME subtype of C4 in FLs and revealed differential transcript abundance of several potential mobile regulators and their associated receptors or transporters in two developmentally different hypocotyls of H. mollissima Bunge. These differentially expressed genes (DEGs) belong to diverse functional groups, including various transcription factor (TF) families, phytohormones metabolism, and signaling peptides, part of which could be related to hypocotyl development. Our findings support the higher nitrogen and water use efficiency associated with C4 photosynthetic and provide insights into the coordinated above- and under-ground tissue communication during the developmental transition of C3 to C4 photosynthesis in this species.

plant biology↗