Biomedical subjects

Saumya Das

Publications and source records attributed to Saumya Das.

4 recordsLinked to original sources

PubMed2025

AstroGreen transgenic mouse illuminates the trafficking of astrocyte-derived extracellular vesicles.

Astrocytes interact with neighboring cells by releasing extracellular vesicles (EVs). Tools to study astrocyte EV-mediated communication with other brain cells in vivo are essential. In this study, we crossed the Exomap1 transgenic mouse expressing Cre-activated human-specific CD81 (HsCD81) fused to the fluorescent protein mNeonGreen (HsCD81mNG), to a transgenic mouse expressing Cre under the astrocyte-expressing GFAP promoter resulting in Exomap1::Gfap-Cre mice, referred to here as AstroGreen. We characterized HsCD81mNG-expressing astrocytes and shedded EVs loaded with HsCD81mNG and Cre, both in vitro and in mouse brains. Using this model, we show that HsCD81mNG can be used to track EV content, production, and functional Cre transfer in vitro and in the brain, allowing evaluation of the interaction of astrocytes with neighboring cells mediated by EVs. We anticipate that this model will improve our understanding of astrocytes transferring EVs within their surroundings during normal physiological processes and in the context of neuropathological conditions.

Animals↗

PubMed2025

A hypoxia-responsive tRNA-derived small RNA confers renal protection through RNA autophagy.

Transfer RNA-derived small RNAs (tsRNAs or tDRs) perform a range of cellular functions. Here, we showed that tRNA-Asp-GTC-3'tDR, a hypoxia-induced tDR derived from the 3' end of tRNA-Asp-GTC, activated autophagic flux in kidney cells and its silencing blocked autophagic flux. Functional gain-/loss-of-function studies in murine kidney disease models demonstrated a substantial renoprotective function of tRNA-Asp-GTC-3'tDR. Mechanistically, tRNA-Asp-GTC-3'tDR assembled stable G-quadruplex structures and sequestered pseudouridine synthase 7 (PUS7), preventing catalytic pseudouridylation of histone mRNAs. The resulting pseudouridylation deficiency directed histone mRNAs to the autophagosome-lysosome pathway, triggering RNA autophagy. This tDR-induced RNA autophagy pathway was activated during murine and human kidney diseases, suggesting clinical relevance. Thus, tRNA-Asp-GTC-3'tDR plays a role in regulating RNA autophagy, which helps to maintain homeostasis in kidney cells and protects against kidney injury.

Animals↗

PubMed2025

The extracellular vesicle transcriptome provides tissue-specific functional genomic annotation relevant to disease susceptibility in obesity.

We characterized circulating extracellular vesicles (EVs) in obese and lean humans, identifying transcriptional cargo differentially expressed in obesity (277 unique genes; false discovery rate < 10%). Since circulating EVs may have broad origin, we compared this obesity EV transcriptome with expression from human visceral-adipose-tissue-derived EVs from freshly collected and cultured biopsies from the same obese individuals, observing high concordance. Using a comprehensive set of adipose-specific epigenomic and chromatin conformation assays, we found that the differentially expressed transcripts from the EVs were those regulated in adipose by body mass index-associated SNPs (p < 5 × 10-8) from a large-scale genome-wide association study (GWAS). Using a phenome-wide association study of the regulatory SNPs for the EV-derived transcripts, we identified a substantial enrichment for inflammatory phenotypes, including type 2 diabetes. Collectively, these findings represent the convergence of the GWAS (genetics), epigenomics (transcript regulation), and EV (liquid biopsy) fields, enabling powerful future genomic studies of complex diseases.

Humans↗

PubMed2024

Self-quenched tRNA reporters for imaging tRNA-derived RNA biogenesis.

tRNA-derived small RNAs (tDRs) are an emerging class of small non-coding RNAs that play crucial roles in various cellular processes. However, there is a paucity of data on their sub-cellular localization due to a lack of tools and reagents to image tDRs. Imaging tDRs remains challenging due to the similar sequences between tDR and its parent tRNA. Here, we describe an innovative tool for studying the formation and localization of tDRs in various biological processes using a self-quenched tDR biogenesis reporter. This method utilizes a full-length tRNA molecule conjugated with both fluorescence and quencher groups at 5'- and 3'- ends. In its intact state, the fluorescence is quenched. Upon cleavage by specific ribonucleases and strand separation, the fluorescence becomes detectable, allowing real-time imaging of tDR biogenesis. This protocol details the design, synthesis, and application of this reporter, including transfection procedures and imaging techniques. The method offers a powerful approach for investigating tDR dynamics in living cells, providing insights into their roles in cellular processes and stress responses.

RNA, Transfer↗