Biology subjects

Suryawanshi, H.

Publications and source records attributed to Suryawanshi, H..

3 recordsLinked to original sources

bioRxiv2018

Insights from Comparison of the Renal and Skin Single Cell Transcriptomes in Lupus Nephritis

Lupus nephritis (LN) occurs in up to 50% of patients with systemic lupus erythematosus (SLE), and is a major contributor to mortality and morbidity. LN presents as a highly heterogeneous disease both in histopathology and response to therapy. The molecular and cellular processes leading to renal damage and to the heterogeneity of the disease are not well understood. To elucidate the processes underpinning the heterogeneity of LN, we applied singlecell RNA-sequencing (scRNA-seq) to renal biopsies from LN patients. Skin biopsies were evaluated as a source of biomarkers for monitoring kidney disease. Type-I interferon (IFN) response signatures were identified in tubular cells and keratinocytes, differentiating LN patients from healthy controls. Non-responders associated with higher IFN signatures in both tissue compartments. Moreover, non-response was also associated with a fibrotic signature in the tubular cells. Receptor-ligand interaction analysis indicated that the fibrotic process is likely mediated by FGF receptors with the initiating signal originating from infiltrating leukocytes. Differential expression analysis of tubular cells between proliferative and membranous LN pointed to several fibrosis-relevant pathways, which may offer insight into their histological differences. In summary, scRNA-seq was applied to LN to deconstruct its heterogeneity and provide novel targets for personalized approaches to therapy.

immunology↗

bioRxiv2017

Insights into regeneration from the genome, transcriptome and metagenome analysis of Eisenia fetida

Earthworms show a wide spectrum of regenerative potential with certain species like Eisenia fetida capable of regenerating more than two-thirds of their body while other closely related species, such as Paranais litoralis seem to have lost this ability. Earthworms belong to the phylum annelida, in which the genomes of the marine oligochaete Capitella telata, and the freshwater leech Helobdella robusta have been sequenced and studied. The terrestrial annelids, in spite of their ecological relevance and unique biochemical repertoire, are represented by a single rough genome draft of Eisenia fetida (North American isolate), which suggested that extensive duplications have led to a large number of HOX genes in this annelid. Herein, we report the draft genome sequence of Eisenia fetida (Indian isolate), a terrestrial redworm widely used for vermicomposting assembled using short reads and mate-pair reads. An in-depth analysis of the miRNome of the worm, showed that many miRNA gene families have also undergone extensive duplications. Genes for several important proteins such as sialidases and neurotrophins were identified by RNA sequencing of tissue samples. We also used de novo assembled RNA-Seq data to identify genes that are differentially expressed during regeneration, both in the newly regenerating cells and in the adjacent tissue. Sox4, a master regulator of TGF-beta induced epithelial-mesenchymal transition was induced in the newly regenerated tissue. The regeneration of the ventral nerve cord was also accompanied by the induction of nerve growth factor and neurofilament genes. The metagenome of the worm, characterized using 16S rRNA sequencing, revealed the identity of several bacterial species that reside in the nephridia of the worm. Comparison of the bodywall and cocoon metagenomes showed exclusion of hereditary symbionts in the regenerated tissue. In summary, we present extensive genome, transcriptome and metagenome data to establish the transcriptome and metagenome dynamics during regeneration.

genomics↗

bioRxiv2017

Aminoglycoside Antibiotics Perturb Physiologically Important MicroRNA Contributing To Drug Toxicity

miRNAs are key non-protein coding regulators of gene expression in various pathophysiological conditions. Targeting miRNA with small molecules offer an unconventional approach, where clinically active compounds with RNA binding activity can be tested for their ability to modulate miRNA levels and thus for drug repositioning. Aminoglycoside antibiotics are highly effective microbicidal RNA binding molecules that bind to prokaryotic rRNA secondary structures. Here, we report that specific subsets of miRNA can be modulated by aminoglycosides. However, ototoxicity (cochlear and vestibular) and nephrotoxicity of multiple origins resulting from prolonged use are a well-known disadvantage of aminoglycosides. Mature non-coding RNAs and their precursors can present off-target sites, by forming secondary structures that resemble ribosomal RNA, thus providing an additional molecular basis for the toxicity of aminoglycosides. Using in vitro, in cellulae and physiological responses, we provide evidence for the direct functional perturbation of the miR- 96 cluster leading to selective cell death in neuromasts- the zebrafish equivalent of cochlear hair cells, by Streptomycin, a prototype aminoglycoside antibiotic, thus contributing to the observed ototoxicity. Our observations, collectively underscore the importance of re- evaluating RNA binding drugs for their off-targeting effects in the context of miRNA and other functional non-coding RNA.

cell biology↗