Biology subjects

Farhat, S.

Publications and source records attributed to Farhat, S..

5 recordsLinked to original sources

bioRxiv2024

Cellular and molecular changes in the human osteoarthritic and aging hip pulvinar

Osteoarthritis (OA) represents a multifaceted pathology characterized by intricate signaling across various joint tissues, where the sub-synovial adipose tissue (ssAT) has been suggested to play diverse roles, from serving as a stem cell reservoir, mechanosensing, serving as a neuroendocrine organ, to modulating inflammation. In this study, we aimed to uncouple the cellular and molecular alterations within the human hip ssAT (the pulvinar) linked to OA and aging, elucidating the distinct contributions of disease onset and progression versus normal aging. Our findings show a pronounced increase in mesenchymal stem/progenitor cells (MSPCs) in the osteoarthritic pulvinar, associated with the upregulation of putative MSPC markers (DPP4, and THY1), indicating an adaptive repair response. Concurrently, in OA patients we observed an altered immune landscape featuring reduced innate immune cells and elevated exhausted CD8+ cells, along with upregulation of genes critical for inflammation and fibroblast activation. Our findings reveal a nuanced picture of OA, where increased stem cell numbers and vascularization, combined with specific gene expression patterns differentiate OA from normal aging. This study not only delineates the roles of inflammation, immune regulation, and stem cell activity in the OA pulvinar but also identifies potential therapeutic targets to modulate these pathways, offering novel insights into OA as a complex interplay of degenerative and intrinsic tissue repair.

physiology↗

bioRxiv2023

Self-renewing Sox9+ osteochondral stem cells in the postnatal skeleton

Postnatal skeletal growth, homeostatic maintenance, and regeneration is driven by skeletal stem cells. In addition, it is well established that skeletal tissues lose their regenerative potential with age, comorbidities, and repeated trauma, possibly through stem cell exhaustion or loss of function. However, it is largely unknown where these cells reside in skeletal tissues, what molecular mechanisms regulate their self-renewal and fate decisions, and how to isolate, purify, and expand them ex vivo. Therefore, there is an urgent need for a deeper understanding of postnatal skeletal stem cells. Here, we used genetic lineage tracing, thymidine analogues retention, whole bone microscopy, imaging cytometry, in vitro assays, and single cell transcriptomics and provide the first experimental evidence for the existence of self-renewing osteochondral stem cells in the postnatal skeleton in both males and females. We also show direct comparisons between adult, fetal, mouse, and human skeletal stem cells at the transcriptome level.

developmental biology↗

bioRxiv2022

Chromosomal assembly of the flat oyster (Ostrea edulis L.) genome as a new genetic ressource for aquaculture

The European flat oyster (Ostrea edulis L.) is the endemic species of the European coasts. Its exploitation has been reduced during the last decades, because of the appearance of two parasites that have led to the collapse of the stocks and the strong decline of the natural oyster beds. O. edulis has been the subject of numerous studies and programs in population genetics and on the presence of the parasites Bonamia ostreae and Marteilia refringens. These studies investigated the effects of these parasites mainly on immunity at the molecular and cellular levels. Several genetic selection programs especially related to resistance to the parasite have been initiated. Within the framework of a European project (PERLE 2) which aims to produce genetic lines of O. edulis with hardiness traits (growth, survival, resistance) for the purpose of repopulating natural oyster beds in Brittany and reviving the culture of this species on the foreshore, obtaining a reference genome has proved to be essential as done recently in many bivalve species of aquaculture interest. Here, we present a chromosome-level genome assembly and annotation for the European flat oyster, generated by combining PacBio technology, Illumina, 10X linked and Hi-C sequencing. The finished assembly is 887.2 Mb with a scaffold-N50 of 97.1 Mb scaffolded on the expected 10 pseudo-chromosomes. Annotation of the genome revealed the presence of 35962 protein-coding genes. We analyzed in details the transposable elements (TE) diversity in the flat oyster genome, highlight some specificities in tRNA and miRNA composition and provide first insights in the molecular response of O. edulis to M. refringens. This genome will serve as a reference for genomic studies on O. edulis to better understand its basic physiology or developing genetic markers in breeding projects for aquaculture or natural reef restoration.

genomics↗

bioRxiv2020

Quantitative 3D Imaging of the Cranial Microvascular Environment at Single-Cell Resolution

Vascularization is critical for skull development, maintenance, and healing. Yet, there remains a significant knowledge gap in the relationship of blood vessels to cranial skeletal progenitors during these processes. Here, we introduce a quantitative 3D imaging platform to enable visualization and analysis of high-resolution datasets (>100 GB) throughout the entire murine calvarium. Using this technique, we provide single-cell resolution 3D maps of vessel phenotypes and skeletal progenitors in the frontoparietal cranial bones. Through these high-resolution datasets, we demonstrate that CD31hiEmcnhi vessels are spatially correlated with both Osterix+ and Gli1+ skeletal progenitors during postnatal growth, healing, and stimulated remodeling, and are concentrated at transcortical canals and osteogenic fronts. Interestingly, this relationship was weakened in mice with a conditional knockout of PDGF-BB in TRAP+ osteoclasts, suggesting a potential role for osteoclasts in maintaining the native cranial microvascular environment. Our findings provide a foundational framework for understanding how blood vessels and skeletal progenitors spatially interact in cranial bone, and will enable more targeted studies into the mechanisms of skull disease pathologies and treatments. Additionally, our technique can be readily adapted to study numerous cell types and investigate other elusive phenomena in cranial bone biology.

bioengineering↗

bioRxiv2020

Developing human fetal skin demonstrates a unique lymphocyte signature

Lymphocytes in barrier tissues play critical roles in host defense and homeostasis. These cells take up residence in tissues during defined developmental windows, when they may demonstrate distinct phenotypes and functions. Here, we utilized mass and flow cytometry to elucidate early features of human skin immunity, demonstrating a unique fetal skin lymphocyte signature. While most conventional {beta} T (Tconv) cells in fetal skin have a naive, proliferative phenotype, a subset of CD4+ Tconv and CD8+ cells demonstrate memory-like features and a propensity for IFN{gamma} production. Skin regulatory T cells dynamically accumulate over the second trimester in temporal and regional association with hair follicle development. These fetal skin Tregs demonstrate an effector memory phenotype while differing from their adult counterparts in expression of key effector molecules. Thus, we identify features of prenatal skin lymphocytes that may have key implications for understanding antigen and allergen encounters in utero and in infancy.

immunology↗