Biology subjects

Autissier, P.

Publications and source records attributed to Autissier, P..

4 recordsLinked to original sources

bioRxiv2026

The increased production of monocytes with immunosuppressive transcriptional profiles predicts the development of SIV encephalitis

HIV-associated neurocognitive disorders (HAND) remain common despite antiretroviral therapy. We previously demonstrated that increased percentages of newly generated BrdU-labeled (BrdU+) monocytes predict AIDS progression and SIV encephalitis (SIVE) as early as 8 and consistently by 21 days post-infection (DPI) in SIV-infected macaques, but their molecular identity remained unknown. We performed Bulk RNA sequencing of FACS-sorted BrdU+ and BrdU- monocytes from uninfected animals and SIV-infected macaques at 21 DPI and necropsies, including SIVE or not (SIVnoE). BrdU+ monocytes underwent progressive transcriptional remodeling during SIV infection. Early SIVE-predictive monocytes exhibited suppressed interferon, TNF-/NF-{kappa}B, antigen-presentation, and antimicrobial pathways, with increased LILRB4 and PARP2 expression. At terminal disease, SIVE BrdU+ monocytes displayed an immunosuppressive profile, reduced HLA-DR expression, and increased structural variants compared with SIVnoE monocytes. Together, newly generated circulating monocytes in animals progressing to SIVE are an immature and immunosuppressive population that emerges before neuropathology, implicating dysregulated monocytopoiesis and pathogenic monocytes in HAND.

immunology↗

bioRxiv2023

CRISPR-Hybrid: A CRISPR-Mediated Intracellular Directed Evolution Platform for RNA Aptamers

Recent advances in gene editing and precise regulation of gene expression based on CRISPR technologies have provided powerful tools for the understanding and manipulation of gene functions. Fusing RNA aptamers to the sgRNA of CRISPR can recruit cognate RNA-binding protein (RBP) effectors to target genomic sites, and the expression of sgRNA containing different RNA aptamers permit simultaneous multiplexed and multifunctional gene regulations. Here, we report an intracellular directed evolution platform for RNA aptamers against intracellularly expressed RBPs. We optimized a bacterial CRISPR-hybrid system coupled with FACS, and identified novel high affinity RNA aptamers orthogonal to existing aptamer-RBP pairs. Application of orthogonal aptamer-RBP pairs in multiplexed CRISPR allowed effective simultaneous transcriptional activation and repression of endogenous genes in mammalian cells.

synthetic biology↗

bioRxiv2018

Monocyte Infection Dynamics Shape HIV-1 Phyloanatomy in the Peripheral Blood

Human immunodeficiency virus (HIV) RNA and DNA have been isolated from patient monocytes, an immune cell population that is quite different in several aspects from the canonical T-cell viral target. Because monocytes are migratory and resilient to both natural and synthetic antiviral defenses, knowledge of the contribution of monocyte infection to ongoing viral evolution and spread in vivo is of significant interest for drug development and treatment strategies. Using single viral genome sequencing from different peripheral blood compartments and phyloanatomic statistical inference, we demonstrate that productively infected monocytes follow an evolutionary trajectory that is distinct from peripheral T cells during multiple stages of disease progression. Gene flow and selection analysis reveal plasticity in the source of monocyte infection and in the region of the HIV envelope glycoprotein that experiences selection pressure across individuals. The findings, thus, point to a potential reservoir showing a range of infection and transmission dynamics, for which the current universal, T cell-targeted treatment strategies would be inadequate.\n\nAuthor summaryHuman immunodeficiency virus is a rapidly evolving virus, allowing its genetic material to act as a fingerprint for epidemiological processes among, as well as within, individual infected hosts. In this study, sampling of viral RNA from plasma and differing infected immune cell populations from the peripheral blood was undertaken for three separate individuals in order to infer such processes. The results revealed a productively infected monocyte cell population, for which distinct selection pressures were linked to differing spatiotemporal origins of infection. In light of previous evidence of the migratory nature of these cells and resilience to both natural and synthetic antiviral defenses, this study underscores the importance of further investigation into the role of monocytes, and monocyte-rich tissues, as viral reservoirs during treatment of HIV with antiretroviral therapy.

evolutionary biology↗

bioRxiv2018

Characterizing smoking-induced transcriptional heterogeneity in the human bronchial epithelium at single-cell resolution

The human bronchial epithelium is composed of multiple, distinct cell types that cooperate to perform functions, such as mucociliary clearance, that defend against environmental insults. While studies have shown that smoking alters bronchial epithelial function and morphology, the precise effects of this exposure on specific cell types are not well-understood. We used single-cell RNA sequencing to profile bronchial epithelial cells from six never- and six current smokers. Unsupervised analyses identified thirteen cell clusters defined by unique combinations of nineteen distinct gene sets. Expression of a set of toxin metabolism genes localized to ciliated cells from smokers. Smoking-induced airway remodeling was characterized by a loss of club cells and extensive goblet cell hyperplasia. Finally, we identified a novel peri-goblet epithelial subpopulation in smokers that expressed a marker of bronchial premalignant lesions. Our data demonstrates that smoke exposure drives a complex landscape of cellular and molecular alterations in the human bronchial epithelium that may contribute to the onset of smoking-associated lung diseases.

genomics↗