Biology subjects

Pietrosemoli, N.

Publications and source records attributed to Pietrosemoli, N..

4 recordsLinked to original sources

bioRxiv2026

Stress-responsive Mycobacterium tuberculosis subpopulations manipulate macrophage polarization and can be targeted to limit inflammation

Tuberculosis is characterized by broad clinical heterogeneity that hinders infection control, with differences in lesion development, progression, and treatment outcomes. This complexity is likely associated with Mycobacterium tuberculosis inherent phenotypic variation and its capacity to diversify under host microenvironmental and antimicrobial stressors. Here, we analyze M. tuberculosis at the single-cell and subpopulation level using fluorescent reporters, imaging, transcriptomic, and functional assays. We identify RNA signatures specific to stress-responsive bacilli with translational potential. Focusing on the clinically validated chaperone GroEL2, we find that it correlates with M. tuberculosis growth rate and stress tolerance in vitro and intracellularly. Furthermore, GroEL2 phenotypic diversity influences innate responses in macrophages, which experience different polarization, in turn affecting GroEL2 expression. We also show that targeting GroEL2 impairs pathogen survival and dampens inflammation. This study provides a link between pathogen phenotypic variation and macrophage fates, with implications for early infection outcomes, local disease progression, and subpopulation-targeted interventions.

microbiology↗

bioRxiv2024

IL-23 tunes inflammatory functions of human mucosal-associated invariant T (MAIT) cells

IL-23 signaling plays a key role in the pathogenesis of chronic inflammatory and infectious diseases, yet the cellular targets and signaling pathways affected by this cytokine remain poorly understood. We show that IL-23 receptors are expressed on the large majority of human MAIT, but not of conventional T cells. Protein and transcriptional profiling at the population and single cell level demonstrates that stimulation with IL-23 or the structurally related cytokine IL-12 drives distinct functional profiles, revealing a high level of plasticity of MAIT cells. IL-23, in particular, affects key molecules and pathways related to autoimmunity and cytotoxic functions. Integrated analysis of transcriptomic and chromatin accessibility, supported by CRISPR/Cas9 mediated deletion, shows that AP-1 transcription factors constitute a key regulatory node of the IL-23 pathway in MAIT cells. In conclusion, our findings indicate that MAIT cells are key mediators of IL-23 functions in immunity to infections and chronic inflammatory diseases.

immunology↗

bioRxiv2023

Transcriptome profiling of human colonic cells exposed to the gut pathobiont Streptococcus gallolyticus subsp. gallolyticus.

Streptococcus gallolyticus sp. gallolyticus (SGG) is a gut pathobiont involved in the development of colorectal cancer (CRC). To decipher the contribution of SGG in tumor initiation and/or acceleration respectively, a global transcriptome was performed in normal colonic cells (FHC) and in tumoral colonic cells (HT29). To identify SGG-specific alterations, we chose the phylogenetically closest relative, Streptococcus gallolyticus subsp. macedonicus (SGM) as the control bacterium. We show that SGM, a bacterium generally considered as safe, did not induce any transcriptional changes on the two human colonic cells. The transcriptional reprogramming induced by SGG was significantly different in FHC and HT29 cells, with most of the up- and down-regulated genes associated with cancer disease. Top up-regulated genes related to cancer were: (i) IL-20, CLK1, SORBS2, ERG1, PIM1, SNORD3A for normal FHC cells and (ii) TSLP, BHLHA15, LAMP3, ZNF27B, KRT17, ATF3 for cancerous HT29 cells. SGG induces much stronger transcriptional changes in cancerous than in normal colonic cells (2,090 vs 128 genes being affected, respectively). Gene set enrichment analysis reveals that SGG-induced strong ER- (endoplasmic reticulum) stress and UPR- (unfolded protein response) activation in colonic epithelial cells. Our results suggest that SGG induces a pro-tumoral shift in human colonic cells, particularly in transformed cells potentially accelerating tumor development in the colon.

microbiology↗

bioRxiv2017

Comparison of multiple transcriptomes exposes unified and divergent features of quiescent and activated skeletal muscle stem cells

BackgroundSkeletal muscle stem cells (MuSCs) are quiescent in adult mice and can undergo multiple rounds of proliferation and self-renewal following muscle injury. Several labs have profiled transcripts of myogenic cells during developmental and adult myogenesis with the aim of identifying quiescent markers. Here, we focused on the quiescent cell state and generated new transcriptome profiles that include subfractionations of adult MuSC populations, and an artificially induced prenatal quiescent state, to identify core signatures for quiescent and proliferating MuSCs.\n\nMethodsComparison of available data offered challenges related to the inherent diversity of datasets and biological conditions. We developed a standardized workflow to homogenize the normalization, filtering, quality control steps for the analysis of gene expression profiles allowing the identification up- and down-regulated genes and the subsequent gene set enrichment analysis. To share the analytical pipeline of this work, we developed Sherpa, an interactive Shiny server that allows multiscale comparisons for extraction of desired gene sets from the analysed datasets. This tool is adaptable to cell populations in other contexts and tissues.\n\nResultsA multiscale analysis comprising eight datasets of quiescent MuSCs had 207 and 542 genes commonly up- and down-regulated, respectively. Shared up-regulated gene sets include an over-representation of the TNFa pathway via NFKb signaling, Il6-Jak-Stat3 signaling, and the apical surface processes, while shared down-regulated gene sets exhibited an over-representation of Myc and E2F targets, and genes associated to the G2M checkpoint and oxidative phosphorylation. However, virtually all datasets contained genes that are associated with activation or cell cycle entry, such as the immediate early stress response genes Fos and Jun. Empirical examination of fixed and isolated MuSCs showed that these and other genes were absent in vivo, but activated during procedural isolation of cells.\n\nConclusionsThrough the systematic comparison and individual analysis of diverse transcriptomic profiles, we identified genes that were consistently differentially expressed among the different datasets and common underlying biological processes key to the quiescent cell state. Our findings provide impetus to define and distinguish transcripts associated with true in vivo quiescence from those that are first responding genes due to disruption of the stem cell niche.

cell biology↗