Biology subjects

Majd, A.

Publications and source records attributed to Majd, A..

3 recordsLinked to original sources

bioRxiv2026

Scalable longitudinal imaging and transcriptomics of cells in dynamic enclosures

Dynamic transitions between cell states underlie both normal physiology and disease. However, most single-cell technologies capture only static snapshots. To address this gap, we developed a platform that integrates light-guided hydrogel polymerization with computer vision to generate on-demand compartments around live cells, enabling longitudinal imaging of cellular behavior paired with whole-transcriptome profiling of the same cells at scale. These data link dynamic phenotypes with molecular programs, enabling deeper characterization of cellular states. This approach revealed an adaptive, drug-resistant state in lung cancer cells characterized by potassium channel upregulation and p53-dependent quiescence. In models of adipogenesis and microglial phagocytosis, joint analysis of imaging and transcriptomic data identified key drivers of cellular function that were missed by transcriptomic clustering alone. These results establish the value of paired functional and transcriptomic analysis to resolve molecular drivers of complex cellular behaviors.

systems biology↗

bioRxiv2024

Distinct differentiation trajectories leave lasting impacts on gene regulation and function of V2a interneurons

During development, early regionalization segregates lineages and directs diverse cell fates. Sometimes, however, distinct progenitors produce analogous cell types. For example, V2a neurons, are excitatory interneurons that emerge from different anteroposterior progenitors. V2a neurons demonstrate remarkable plasticity after spinal cord injury and improve motor function, showing potential for cell therapy. To examine how lineage origins shape their properties, we differentiated V2a neurons from hPSC-derived progenitors with distinct anteroposterior identities. Single-nucleus multiomic analysis revealed lineage-specific transcription factor motifs and numerous differentially expressed genes related to axon growth and calcium handling. Bypassing lineage patterning via transcription factor-induced differentiation yielded neurons distinct from both developmentally relevant populations and human tissue, emphasizing the need to follow developmental steps to generate authentic cell identities. Using in silico and in vitro loss-of-function analyses, we identified CREB5 and TCF7L2 as regulators specific to posterior identities, underscoring the critical role of lieage origins in determining cell states and functions.

developmental biology↗

bioRxiv2023

Inhibition of muscarinic receptor signaling protects human enteric inhibitory neurons against platin chemotherapy toxicity

GI toxicity is a common dose-limiting adverse effect of platin chemotherapy treatment. Up to 50% of cancer survivors continue to experience symptoms of chronic constipation or diarrhea induced by their chemotherapy for many years after their treatment. This drug toxicity is largely attributed to damage to enteric neurons that innervate the GI tract and control GI motility. The mechanisms responsible for platin-induced enteric neurotoxicity and potential preventative strategies have remained unknown. Here, we use human pluripotent stem cell derived enteric neurons to establish a new model system capable of uncovering the mechanism of platin-induced enteric neuropathy. Utilizing this scalable system, we performed a high throughput screen and identified drug candidates and pathways involved in the disease. Our analyses revealed that excitotoxicity through muscarinic cholinergic signaling is a key driver of platin-induced enteric neuropathy. Using single nuclei transcriptomics and functional assays, we discovered that this disease mechanism leads to increased susceptibility of specific neuronal subtypes, including inhibitory nitrergic neurons, to platins. Histological assessment of the enteric nervous system in platin-treated patients confirmed the selective loss of nitrergic neurons. Finally, we demonstrated that pharmacological and genetic inhibition of muscarinic cholinergic signaling is sufficient to rescue enteric neurons from platin excitotoxicity in vitro and can prevent platin-induced constipation and degeneration of nitrergic neurons in mice. These studies define the mechanisms of platin-induced enteric neuropathy and serve as a framework for uncovering cell type-specific manifestations of cellular stress underlying numerous intractable peripheral neuropathies.

pharmacology and toxicology↗