Biology subjects

Tayler, I.

Publications and source records attributed to Tayler, I..

2 recordsLinked to original sources

bioRxiv2025

Matrix stiffness and stress relaxation regulate osteogenesis through histone demethylases KDM4B and KDM6B

Stem cells sense biophysical cues within their extracellular microenvironment and respond via mechanotransduction signaling pathways that induce changes in gene expression and associated cell fate outcomes. Histone modifying enzymes are known to drive stem cell differentiation through changes in chromatin accessibility, but little is understood as to how extracellular matrix (ECM) mechanics regulate epigenomic remodeling. Here, we utilize alginate hydrogels with tunable mechanical properties to investigate the role of both matrix stiffness and viscoelasticity on histone demethylase expression and activity during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Our results reveal that the expression of two histone demethylases, KDM4B and KDM6B, are upregulated during osteogenesis in response to stiff, viscoelastic matrix conditions. Inhibition of mechanotransduction signaling pathways reduces expression of KDM4B and KDM6B and hinders osteogenic differentiation overall. Interestingly, phosphorylation of SMAD 1/5/8 was shown to increase in cells cultured in stiff, stress relaxing matrices, and pharmacological inhibition of SMAD 1/5/8 activation reduced expression of KDM4B and KDM6B and decreased osteogenic differentiation. Taken together, our results reveal novel impacts of stem cell mechanotransduction signaling events that promote osteogenesis through epigenetic remodeling.

cell biology↗

bioRxiv2021

High performance microbial opsins for spatially and temporally precise perturbations of large neuronal networks

Patterned optogenetic activation of defined neuronal populations in the intact brain can reveal fundamental aspects of the neural codes of perception and behavior. The biophysical properties of existing optogenetic tools, however, constrain the scale, speed, and fidelity of precise optical control. Here we use structure-guided mutagenesis to engineer opsins that exhibit very high potency while retaining fast kinetics. These new opsins enable large-scale, temporally and spatially precise control of population neural activity in vivo and in vitro. We benchmark these new opsins against existing optogenetics tools with whole-cell electrophysiology and all-optical physiology and provide a detailed biophysical characterization of a diverse family of microbial opsins under two-photon illumination. This establishes a toolkit and a resource for matching the optimal opsin to the goals and constraints of patterned optogenetics experiments. Finally, by combining these new opsins with optimized procedures for cell-specific holographic photo-stimulation, we demonstrate the simultaneous co-activation of several hundred spatially defined neurons with a single hologram, and nearly double that number by temporally interleaving holograms at fast rates. These newly engineered opsins substantially extend the capabilities of patterned illumination optogenetic paradigms for addressing neural circuits and behavior.

neuroscience↗