Biology subjects

Dolga, A.

Publications and source records attributed to Dolga, A..

2 recordsLinked to original sources

bioRxiv2023

Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction

Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves a switch from oxidative phosphorylation (OXPHOS) to glycolysis, or alterations in other metabolic pathways. However, most of the experimental findings have been acquired in murine immune cells and little is known about the metabolic reprogramming of human microglia. In this study, we investigated the transcriptomic and metabolic profiles of mouse and iPSC-derived human microglia challenged with the TLR4 agonist LPS. We found that both species displayed a metabolic shift and an overall increased glycolytic gene signature in response to LPS treatment. The metabolic reprogramming was characterized by the upregulation of hexokinases in mouse microglia and phosphofructokinases in human microglia. This study provides the first direct comparison of energy metabolism between mouse and human microglia, highlighting the species-specific pathways involved in immunometabolism and the importance of considering these differences in translational research.

cell biology↗

bioRxiv2022

Differentiation of airway cholinergic neurons from human pluripotent stem cells for airway neurobiology studies

Airway cholinergic nerves play a key role in airway physiology and disease. In asthma and other diseases of the respiratory tract, airway cholinergic neurons undergo plasticity and contribute to airway hyperresponsiveness and mucus secretion. We currently lack mechanistic understanding of airway cholinergic neuroplasticity due to the absence of human in vitro models. Here, we developed the first human in vitro model for airway cholinergic neurons using human pluripotent stem cell (hPSC) technology. hPSCs were differentiated towards mature and functional airway cholinergic neurons via a vagal precursor. Airway cholinergic neurons were characterized by ChAT and VAChT expression, and responded to chemical stimulation with changes in Ca2+ mobilization. Co-culture of hPSC-derived airway cholinergic neurons with airway smooth muscle cells enhanced phenotypic and functional characteristics of these neurons. The differentiation protocol we developed for human airway cholinergic neurons from hPSCs allows for studies into airway neurobiology and airway neuroplasticity in disease.

neuroscience↗