Biology subjects

Masarapu, Y.

Publications and source records attributed to Masarapu, Y..

3 recordsLinked to original sources

bioRxiv2025

A molecular atlas of cell-type specific signatures in the parkinsonian striatum.

The progressive degeneration of dopaminergic projections to the striatum is a key disease mechanism in Parkinsons disease (PD). To define the cellular landscape in the parkinsonian striatum, we mapped the cell-type specific transcriptional landscape in early and progressive PD mouse models and in human PD stages. Our analyses revealed substantial transcriptomic changes across both neuronal and glial populations, with astrocytes and oligodendrocytes exhibiting distinct disease-associated gene expression profiles. Notably, progressive dopamine depletion uncovered differential neuronal vulnerability, identifying eccentric striatal projection neurons (SPNs) and Chst9-expressing direct-pathway SPNs as among the most resilient subtypes in both species. This cross-species resource establishes a comprehensive framework for investigating cell-state dynamics in the parkinsonian striatum and uncovers selectively vulnerable and resistant cell types that can inspire new therapeutic strategies.

neuroscience↗

bioRxiv2022

Miniature spatial transcriptomics for studying parasite-endosymbiont relationships at the micro scale

Several important human infectious diseases are caused by microscale-sized parasitic nematodes like filarial worms. Filarial worms have their own spatial tissue organization and to uncover this tissue structure, we need methods that can spatially resolve these miniature specimens. Most filarial worms evolved a mutualistic association with endosymbiotic bacteria Wolbachia, however, the mechanisms underlying the dependency of filarial worms on the fitness of these bacteria remain unknown. As Wolbachia is essential for the development, reproduction, and survival of filarial worms, we focused on studying a posterior region containing reproductive tissue and developing embryos of adult female Brugia malayi worms. To spatially explore how Wolbachia interacts with the worms reproductive system, we performed a spatial characterization using Spatial Transcriptomics (ST) across our region of interest. We provide a proof-of-concept for miniature-ST to explore spatial gene expression patterns in small sample types, demonstrating the methods ability to uncover nuanced tissue region expression patterns, observe the spatial localization of key B. malayi - Wolbachia pathway genes, and co-localize the B. malayi spatial transcriptome in Wolbachia tissue regions. We envision our approach to open up new scenarios for the study of infectious diseases caused by micro-scale parasitic worms.

genomics↗

bioRxiv2022

Dual spatially resolved transcriptomics for SARS-CoV-2 host-pathogen colocalization studies in humans

To advance our understanding of cellular host-pathogen interactions, technologies that facilitate the co-capture of both host and pathogen spatial transcriptome information are needed. Here, we present an approach to simultaneously capture host and pathogen spatial gene expression information from the same formalin-fixed paraffin embedded (FFPE) tissue section using the spatial transcriptomics technology. We applied the method to COVID-19 patient lung samples and enabled the dual detection of human and SARS-CoV-2 transcriptomes at 55 m resolution. We validated our spatial detection of SARS-CoV-2 and identified an average specificity of 94.92% in comparison to RNAScope and 82.20% in comparison to in situ sequencing (ISS). COVID-19 tissues showed an upregulation of host immune response, such as increased expression of inflammatory cytokines, lymphocyte and fibroblast markers. Our colocalization analysis revealed that SARS-CoV-2+ spots presented shifts in host RNA metabolism, autophagy, NF{kappa}B, and interferon response pathways. Future applications of our approach will enable new insights into host response to pathogen infection through the simultaneous, unbiased detection of two transcriptomes.

genomics↗