Biology subjects

Hsieh, W.-Y.

Publications and source records attributed to Hsieh, W.-Y..

3 recordsLinked to original sources

bioRxiv2026

SCD-dependent lipid metabolism licenses alternative macrophage activation and macrophage plasticity

Lipid metabolic reprogramming accompanies macrophage activation, yet our understanding of why macrophages profoundly reshape their lipid composition remains unclear. Here, we identify stearoyl-CoA desaturase (SCD) as a lipid-metabolic checkpoint required for the acquisition of the alternatively activated macrophage (AAM) cell state. We show that SCD maintains lipid desaturation balance by ensuring the conversion of newly synthesized saturated long-fatty acids (SFAs) into monounsaturated fatty acids (MUFAs). Critically, disruption of SCD resulted in the rapid accumulation of saturated phosphatidic acid (PA) and hyperactivation of mTORC1, which perturbed the acquisition of stable AAM epigenetic and transcriptional programs. Notably, inhibition of upstream lipogenic enzymes (e.g., ACC and FASN) did not impair AAM polarization, underscoring that an imbalance between newly synthesized saturated and monounsaturated fatty acids, not the loss of de novo lipogenesis, determines AAM identity. Unexpectedly, the loss of SCD redirected IL-4-activated macrophages into an aberrant cell state poised for pro-inflammatory responses, indicating that disruption of this lipid metabolic checkpoint leads to misinterpretation of anti-inflammatory instructional cues. Rescue of SCD-deficient macrophages via mTORC1 inhibition confirmed a causal role for the SCD-PA-mTORC1 axis in controlling macrophage plasticity. Finally, we find that SCD deficiency and resultant PA accumulation attenuated Toxoplasma gondii-driven AAM polarization and reduced pathogen burden. Together, these data establish the SCD-PA lipid signaling axis as a critical metabolic regulator of macrophage plasticity with direct consequences for host defense.

immunology↗

bioRxiv2026

Electrode pooling preserves movement decoding by retaining neural population dynamics

New implantable-electrode fabrication strategies make dense, ultrafine electrode arrays with lower tissue burden increasingly feasible, shifting a key bottleneck for scalable brain-computer interfaces from electrode placement to readout capacity. Electrode pooling, in which multiple electrodes share a readout channel, could relax this bottleneck by combining extracellular signals before acquisition, but it has remained unclear whether such compression preserves the neural population structure needed for behavioral decoding. Here we evaluate this question using software-emulated electrode pooling in mouse sensorimotor cortex during a cue-guided reach-and-grasp task using a high-density microwire array coupled to a CMOS microelectrode-array platform. Pooled recordings retain forelimb kinematic information more effectively than a channel-matched control that discards electrodes. Pooling reduces the separability of electrode-specific spikes and sorted units, indicating a loss of some neuronal detail, but the mixed signals still preserve task-aligned low-dimensional latent dynamics that support decoding. When readout capacity is fixed, this trade-off allows broader electrode coverage to contribute to behaviorally informative population sampling. Together, these results define electrode pooling as a design trade-off for scalable readout, in which some electrode-specific neuronal information is lost but the population dynamics needed for movement decoding remain accessible.

neuroscience↗

bioRxiv2024

IL-4 Licenses B Cell Activation Through Cholesterol Synthesis

Lymphocyte activation involves a transition from quiescence and associated catabolic metabolism to a metabolic state with noted similarities to cancer cells such as heavy reliance on aerobic glycolysis for energy demands and increased nutrient requirements for biomass accumulation and cell division1-3. Following antigen receptor ligation, lymphocytes require spatiotemporally distinct "second signals". These include costimulatory receptor or cytokine signaling, which engage discrete programs that often involve remodeling of organelles and increased nutrient uptake or synthesis to meet changing biochemical demands4-6. One such signaling molecule, IL-4, is a highly pleiotropic cytokine that was first identified as a B cell co-mitogen over 30 years ago7. However, how IL-4 signaling mechanistically supports B cell proliferation is incompletely understood. Here, using single cell RNA sequencing we find that the cholesterol biosynthetic program is transcriptionally upregulated following IL-4 signaling during the early B cell response to influenza virus infection, and is required for B cell activation in vivo. By limiting lipid availability in vitro, we determine cholesterol to be essential for B cells to expand their endoplasmic reticulum, progress through cell cycle, and proliferate. In sum, we demonstrate that the well-known ability of IL-4 to act as a B cell growth factor is through a previously unknown rewiring of specific lipid anabolic programs, relieving sensitivity of cells to environmental nutrient availability.

immunology↗