Biology subjects

Cheung, Y.

Publications and source records attributed to Cheung, Y..

3 recordsLinked to original sources

bioRxiv2024

Skeletal Muscle Stem Cells Modulate Niche Function in Duchenne Muscular Dystrophy through YY1-CCL5 Axis

Stem cell activity is known to be tightly regulated by both intrinsic and extrinsic pathways but less is known about whether and how stem cells modulate their niche microenvironment. Adult skeletal muscle stem cells (MuSCs) are indispensable for muscle regeneration and also tightly regulated by macrophages (MPs) and fibro-adipogenic progenitors (FAPs) in the niche. Deregulated MuSC/MP/FAP interactions and the ensuing inflammation and fibrosis are hallmarks of dystrophic muscle. Here in this study we demonstrate that intrinsic deletion of transcription factor YY1 in MuSCs exacerbates dystrophic pathologies by altering the cellular composition and heterogeneity of MPs and FAPs. Further analysis reveals that the YY1 loss induces the expression of immune genes in MuSCs, including Ccl5. Augmented secretion of CCL5 from MuSCs promotes the recruitment of MPs via CCL5/CCR5 mediated crosstalk, which subsequently hinders the apoptosis and clearance of FAPs through elevated TGF{beta}1 accumulation. Maraviroc mediated pharmacological blockade of the CCL5/CCR5 axis effectively mitigates muscle dystrophy and improves muscle performance. Lastly, we further demonstrate that YY1 represses Ccl5 transcription in MuSCs by directly binding to its enhancer thus facilitating promoter-enhancer looping. Altogether, our study has demonstrated the previously unappreciated role of MuSCs in actively shaping their niche microenvironment through secreting immunomodulatory cytokines, and has also provided novel insight into the therapeutic intervention of muscle dystrophy.

cell biology↗

bioRxiv2022

Timing along the cardiac cycle modulates neural signals of reward-based learning

Natural fluctuations in cardiac activity influence brain activity associated with sensory stimuli and affect perceptual decisions about low magnitude, near-threshold stimuli. However, little is known about the impact of fluctuations in heart activity on other internal representations. Here we investigate cardiac influences on learning-related internal representations - absolute and signed prediction errors. By combining machine learning techniques with electroencephalography (EEG) and both simple, direct indices of task performance and computational model-derived indices of learning, we demonstrate that just as people are more sensitive to low magnitude, near threshold sensory stimuli in certain cardiac phases, so are they more sensitive to low magnitude absolute prediction errors in the same cycles. Importantly, however, this occurs even when the low magnitude prediction errors are associated with clearly suprathreshold sensory events. In addition, participants exhibiting stronger difference in their prediction errors representations between cardiac cycles exhibited higher learning rates and greater task accuracy.

neuroscience↗

bioRxiv2021

Single-cell analysis reveals MHCII expressing keratinocytes in pressure ulcers with worse healing outcomes

Pressure ulcer (PU) is a chronic wound often seen in spinal cord injury patients and other bed-bound individuals, particularly in the elderly population. Despite its association with high mortality, the pathophysiology of PU remains poorly understood. Here, we compared single-cell transcriptomic profiles of human epidermal cells from PU wound edges with those from uninjured skin and acute wounds (AWs) in healthy donors. We identified significant shifts in the cell composition and gene expression patterns in PU. In particular, we found that major histocompatibility complex class II (MHCII) expressing keratinocytes were enriched in patients with worse healing outcomes. Furthermore, we showed that the IFN{gamma} in PU-derived wound fluid could induce MHCII expression in keratinocytes and that these wound fluid-treated keratinocytes inhibited autologous T cell activation. In line with this observation, we found that T cells from PUs enriched with MHCII+ keratinocytes produced fewer inflammatory cytokines. Overall, our study provides a high-resolution molecular map of human PU compared to AW and intact skin, providing new insights into PU pathology and the future development of tailored wound therapy.

genomics↗