Biology subjects

Baskaran, S.

Publications and source records attributed to Baskaran, S..

3 recordsLinked to original sources

bioRxiv2026

Comparative analysis of neuronal proteolytic pathways reveals neuron-specific and sub-compartmental-specific capacities with aging

Proteostasis is essential for maintaining neuronal function, and its dysregulation is a hallmark of aging and neurodegeneration. The ubiquitin-proteasome system (UPS) and macroautophagy are the two major proteolytic pathways responsible for protein degradation. However, their capacity and regulation differ between cell types and across aging. To elucidate the activity of both proteolytic pathways with aging, we performed a comparative analysis of the activity of UPS and macroautophagy in distinct neuronal subcellular compartments, in the cytosol and at synaptic terminals, across aging in neurons of Mus musculus (mouse) and Caenorhabditis elegans (nematode). In mice, our results identified differences between brain areas. While the cortical proteasomal activity declined with aging in both the cytoplasmic as well as synaptic neuronal subcompartments, the cerebellar proteasomal activity decreased only in the cytoplasmic compartment with aging. In C. elegans, we detected a decrease of proteasomal activity in both cytoplasmic and synaptic compartments of neurons. Interestingly, we observed a dysregulation of macroautophagy in both neuronal subcompartments of the cortex and cerebellum in mice as well as in C. elegans neurons with aging. Thus, we uncovered neuron-specific and subcompartmental-specific proteolytic capacities with aging that could manifest in different neuronal vulnerabilities for proteotoxic challenges with aging.

biochemistry↗

bioRxiv2024

Perinatal liver inflammation is associated with persistent elevation of CXCL10 and its canonical receptor CXCR3 on common myeloid progenitors

Biliary atresia (BA) is a leading cause of liver failure in infants. Despite effective surgical drainage, patients with BA exhibit attenuated immune responses to childhood vaccines, suggesting there are long-lasting alterations to immune function. The perinatal liver is home to hematopoietic stem and progenitor cells (HSPCs) and serves as the epicenter for rapidly progressive and significantly morbid inflammatory diseases like BA. We have previously established the role of neonatal myeloid progenitors in the pathogenesis of perinatal liver inflammation (PLI) and hypothesize that PLI leads to long-term changes to HSPCs in mice that recovered from PLI. To test this hypothesis, we compared the changes that occur to HSPCs and mature myeloid populations in the bone marrow of adult mice during homeostasis and during PLI. Our results demonstrate that HSPCs from animals that recover from PLI ("PLI-recovered") undergo long-term expansion with a reduced proliferative capacity. Notably, PLI leads to persistent activation of common myeloid progenitors through the involvement of CXCL10 and its canonical receptor, CXCR3. Our data suggests that the CXCR3-CXCL10 axis may mediate the changes in HSPCs that lead to altered immune function observed in BA, providing support for a targetable pathway to mitigate the detrimental long-term immune effects observed in patients with BA.

immunology↗

bioRxiv2019

Combined mRNA and protein single cell analysis in a dynamic cellular system using SPARC

Combined measurements of mRNA and protein expression in single cells enables in-depth analysis of cellular states. We present single-cell protein and RNA co-profiling (SPARC), an approach to simultaneously measure global mRNA and large sets of intracellular protein in individual cells. Using SPARC, we show that mRNA expression fails to accurately reflect protein abundance at the time of measurement in human embryonic stem cells, although the direction of changes of mRNA and protein expression are in agreement during cellular differentiation. Moreover, protein levels of transcription factors better predict their downstream effects than do the corresponding transcripts. We further show that changes of the balance between protein and mRNA expression levels can be applied to infer expression kinetic trajectories, revealing future states of individual cells. Finally, we highlight that mRNA expression may be more varied among cells than levels of the corresponding proteins. Overall, our results demonstrate that mRNA and protein measurements in single cells provide different and complementary information regarding cell states. Accordingly, SPARC can offer valuable insights in gene expression programs of single cells.

cell biology↗