Biology subjects

Ong, M. T.-Y.

Publications and source records attributed to Ong, M. T.-Y..

2 recordsLinked to original sources

bioRxiv2026

Spatial transcriptomic analysis of myositis muscles reveals novel molecular insights of MDA5+ dermatomyositis

Idiopathic inflammatory myopathies (IIM), also known as myositis, are a rare and heterogeneous group of autoimmune disorders characterized by chronic inflammation of skeletal muscle. Other organs are also frequently affected, such as skin, joints, and lungs, leading to morbidity and even mortality. Anti-MDA5 autoantibody-positive dermatomyositis (MDA5+ DM) is a unique subtype with a high mortality rate but the underlying molecular mechanisms remain incompletely understood. In this study, we profiled the spatial transcriptome of a cohort of healthy controls, MDA5+, and MDA5- muscles and found a distinct transcriptomic profile of the MDA5+ muscles with a low percentage of stressed myofibers but increased immune cell infiltration. Niche analysis revealed a distinct microenvironment in the MDA5+ muscles with the endothelial cell (EC) niche showing increased inflammation, dampened oxygen transport function, and a unique enrichment of the Type 1 interferon response. Cell-cell communication and pathway activity analysis uncovered that hypoxia, TGF-{beta}, NF-{kappa}B, and TNF- signaling were enriched in the MDA5+ EC niche. Altogether, our results support a vasculopathy model whereby blood vessels exhibit a strong inflammatory response and impaired oxygen transport function, leading to vasculopathy and perivascular immune cell infiltration in MDA5+ muscles.

immunology↗

bioRxiv2024

Multiomics mapping and characterization of cellular senescence in aging human muscle uncovers novel senotherapeutics for sarcopenia

Cellular senescence is recognized as a hallmark of organismal aging but how it drives aging particularly in human tissues is not fully understood, partly due to the complex heterogeneous nature of senescence. Here in this study, we leverage single-nucleus multiomics to profile senescence in mononucleated cells of human skeletal muscle and provide the first senescence atlas. We demonstrate the intra-and inter-populational transcriptomic and epigenomic heterogeneity and dynamics of senescence in the cells. We also identify commonalities and variations in senescence-associated secretory phenotypes (SASPs) among the cells and elucidate the function of SASPs in mediating cellular interactions and niche deregulation. Furthermore, we identify targetable SASP factors and demonstrate the possibility of using Maraviroc as a pharmacological senotherapeutic for treating age-associated sarcopenia in muscle. Lastly, we define transcription factors that govern senescence state and SASP induction in aging muscle and elucidate the key function and the underlying mechanism of JUNB in regulating SASP activation in senescent cells. Altogether, our findings demonstrate the prevalence and function of cellular senescence in skeletal muscle and identify a novel pharmacological intervention for sarcopenia.

cell biology↗