Biology subjects

Jahangiri Esfahani, S.

Publications and source records attributed to Jahangiri Esfahani, S..

3 recordsLinked to original sources

bioRxiv2025

Paradoxical Phenotype of Fibromyalgia Neutrophils with Elevated Baseline Inflammation but Blunted Response to Stimulation

Fibromyalgia (FM) is a severe pain condition of unknown etiology. Here, we performed transcriptomics analyses of peripheral neutrophils exposed to an inflammatory stimulus, comparing responses of neutrophils obtained from FM patients versus healthy controls. We observed a state of inflammation in neutrophils from FM patients. However, FM neutrophils were unable to efficiently respond to lipopolysaccharide (LPS). This impairment was especially characteristic of FM patients with no improvement after 5 years after diagnosis in comparison with those who did improve. Blood plasma from FM patients directly stimulated a wide range of primary sensory neurons in vitro and induced pain hypersensitivity when injected into mice. Further analysis identified NF-{kappa}B suppression as a key biological process associated with low-grade inflammation and LPS non-responsiveness in neutrophils from FM patients. The clinically used NF-{kappa}B activator, bryostatin, alleviated hypersensitivity in mice treated with FM plasma, pointing to controlled inflammation induction through reactivation of the NF-{kappa}B pathway as a possible therapeutic target for FM treatment. Our whole blood single-cell RNA sequencing replicated this NF-{kappa}B-driven inflammation observed in bulk analyses transcriptomics in FM patients and revealed that this inflammatory signature is strongly pronounced not only in neutrophils, but across a broad range of immune cells.

molecular biology↗

bioRxiv2023

The Transcriptomics Pain Signature Database

The availability of convenient tools is critical for the efficient analyses of fast-generated omics-wide-level studies. Here, we describe the creation, characterization, and applications of the Pain Signatures Database (TPSDB), a comprehensive database containing the results of differential gene expression analyses from 338 full transcriptomic datasets for pain-related phenotypes. The database allows searching for a specific gene(s), pathway(s), or SNP(s), or downloading the raw data for hypothesis-free analysis. We took advantage of this unique dataset of multiple pain transcriptomics in several ways. The pathway analyses found the cytokine production regulation and innate immune response the most frequently shared pathways across tissues and conditions. A machine learning-based approach across datasets identified RNA biomarkers for inflammatory and neuropathic pain in rodent dorsal root ganglion (DRG) with high certainty. Finally, functional annotation of pain-related GWAS results demonstrated that differentially expressed genes can be more informative than the general tissue-specific genes from DRG or spinal cord in partitioning heritability analyses.

genetics↗

bioRxiv2020

Integrated analysis of high throughput transcriptomic data revealed specific gene expression signature of cardiomyocytes

Acquiring a specific transcriptomic signature of the human and mouse cardiomyocyte (CM) will greatly increase our understanding of their biology and associated diseases that remain the most deadly across the world. In this study, using comprehensive transcriptomic mining of 91 cell types over 877 samples from bulk RNA-sequencing, single cell RNA-sequencing, and microarray techniques, we describe a unique 118-gene signature of human and mouse primary CMs. Once we had access to this CM-specific gene signature, we investigated the spatial heterogeneity of CMs throughout the heart tissue. Moreover, we compared the CM-specific gene signature to that of CMs derived from 10 differentiation protocols, and we identified the protocols that generate cells most similar to primary CMs. Finally, we looked at the specific differences between primary and differentiated CMs and found that differentiated cells underexpress genes related to CM development and maturity. The differentiated cells conversely overexpressed cell cycle-related genes, resulting in the progenitor features that remain in differentiated CMs compared to primary adult CMs. The presence of histone post translational modification H3K27ac from ChIP sequencing data sets were used to confirm transcriptomic findings. To the best of our knowledge, this is the most comprehensive study to date that unravels the unique transcriptomic signature of primary and differentiated CMs. This study provides important insights into our understanding of CM biology and the molecular mechanisms that make them such a unique cell type. Moreover, the specific transcriptomic signature of CMs could be used in developmental studies, stem cell therapy, regenerative medicine, and drug screening assays.

cell biology↗