Biology subjects

Ayyangar, U.

Publications and source records attributed to Ayyangar, U..

3 recordsLinked to original sources

bioRxiv2025

Cell clusters are programmed towards a reductive metabolic 1 state by adherence junctions

Solitary cells form stable clusters via cell-cell adhesion using adherens junctions. The role of these junctions in early cell-state changes as cells form clusters is unclear. Here, we uncover that the formation of cadherin junctions as cells cluster drives a ubiquitous metabolic reprogramming. This reprogramming enhances the pentose phosphate pathway (PPP) and NADPH production to augment a reductive state. Consequently, cell clusters stabilized by cadherin junctions have reduced intracellular reactive oxygen species (ROS), are resistant to exogenous ROS-inducing agents, and have reduced apoptotic markers. Mechanistically, this metabolic reprogramming is driven by the cadherin-dependent activation of NRF2. Blocking the cadherin junction-dependent metabolic program reverses clustered cells to resemble the solitary cell state, increasing cell death and enhancing sensitivity to exogenous ROS. These insights suggest a biochemical basis for adherens junctions mediating a reductive metabolic program as solitary cells form clusters, with implications for understanding multicellular organization and collective cell behavior.

cell biology↗

bioRxiv2022

NeuroWRAP: integrating, validating, and sharing neurodata analysis workflows

Multiphoton calcium imaging is one of the most powerful tools in modern neuroscience. However, multiphoton data require significant pre-processing of images and post-processing of extracted signals. As a result, many algorithms and pipelines have been developed for the analysis of multiphoton data, particularly two-photon imaging data. Most current studies use one of several algorithms and pipelines that are published and publicly available, and add customized upstream and downstream analysis elements to fit the needs of individual researchers. The vast differences in algorithm choices, parameter settings, pipeline composition, and data sources combine to make collaboration difficult, and raise questions about the reproducibility and robustness of experimental results. We present our solution, called NeuroWRAP, which is a tool that wraps multiple published algorithms together, and enables integration of custom algorithms. It enables development of collaborative, shareable custom workflows and reproducible data analysis for multiphoton calcium imaging data enabling easy collaboration between researchers. NeuroWRAP implements an approach to evaluate the sensitivity and robustness of the configured pipelines. When this sensitivity analysis is applied to a crucial step of image analysis, cell segmentation, we find a substantial difference between two popular workflows, CaImAn and Suite2p. NeuroWRAP harnesses this difference by introducing consensus analysis, utilizing two workflows in conjunction to significantly increase the trustworthiness and robustness of cell segmentation results.

neuroscience↗

bioRxiv2022

Epidermis derived lactate promotes sterile inflammation by inducing metabolic rewiring in macrophages.

Dysregulated macrophage responses and changes in tissue metabolism are hallmarks of chronic, sterile inflammation. However, the metabolic cues that direct and support macrophage functions are poorly understood. Here, we show that during sterile inflammation in skin, the epidermis and macrophages uniquely depend on glycolysis and TCA cycle, respectively. This compartment separation is initiated by HIF1a stabilization and enhanced glycolysis in the epidermis. The end product of glycolysis, lactate is exported and utilized by the dermal macrophages to drive their effector functions. Notably, inhibition of lactate mediated crosstalk between the epidermis and macrophages leads to inhibition of sterile inflammation. Overall, our study identifies an essential role for the metabolite lactate in regulating macrophage response that can be effectively targeted to treat skin disorders such as psoriasis. One-Sentence SummaryEpidermis derived lactic acid drives sterile inflammation by augmenting pro-remodeling state in dermal macrophages.

cell biology↗