Biology subjects

Arguel, M.-J.

Publications and source records attributed to Arguel, M.-J..

9 recordsLinked to original sources

bioRxiv2026

Imaging-based spatial isoform transcriptomics resolves transcript diversity at cellular and subcellular resolution

Spatial transcriptomics has transformed our understanding of tissue organization, yet current high-throughput approaches remain largely confined to a gene-centric paradigm, precluding systematic characterization of spatially resolved transcript isoform diversity. Here, we introduce imaging-based spatial isoform transcriptomics (iSiT), a framework enabling simultaneous large-scale gene expression and targeted transcript isoform profiling on the commercial Xenium platform. iSiT resolves alternative splicing events that alter internal transcript structure at cellular and subcellular resolution using a single junction-specific probe per target. To facilitate broader adoption, we developed ProbeHarbour, an open-source toolkit for the design, characterization and management of isoform-specific probes. We demonstrate iSiT in the postnatal mouse brain by combining the Prime 5K gene-level panel with isoform-specific detection of 45 synaptogenesis-associated genes. By extending spatial transcriptomics beyond gene-level measurements, iSiT provides a scalable and readily accessible framework for investigating spatial isoform regulation in development and disease.

neuroscience↗

bioRxiv2026

Life-stage-specific specialities in the cell atlases of the Clytia hemisphaerica planula and medusa

Jellyfish have complex life-cycles, but there has been limited exploration of how this is achieved at the cellular level. We used single-cell transcriptomics to assemble a cell atlas for the planula larva of Clytia hemisphaerica, and compared it to an updated cell atlas for the medusa (jellyfish) stage. The cells of the planula fell into the same broad categories as for the medusa: ectoderm, gastroderm, interstitial cells (i-cells), nematocytes (stinging cells), neurons and secretory cells. Although the planula cells generally showed less diversity than medusae within each category, cells with specialized features unique to their stage could be distinguished by their transcriptional profiles as well as by ultrastructure. Some planula-specific types were identified: aboral secretory cells involved in settlement, and a cell type attributed a role in immunity or post-metamorphic theca production. Distinct transcriptome profiles within different regions of the ciliated planula ectoderm reflected different post-metamorphosis fates of domains along the oral-aboral axis. Inspection of the cell clusters showing significant similarity of marker genes between planula and medusa, and inference of similarity using a statistical model of marker gene presence/absence, revealed correspondences between families of cells from planula and medusa rather than precise cell identities.

evolutionary biology↗

bioRxiv2024

Cell culture differentiation and proliferation conditions influence the in vitro regeneration of the human airway epithelium

The human airway mucociliary epithelium can be recapitulated in vitro using primary cells cultured in an Air-Liquid Interface (ALI), a reliable surrogate to perform pathophysiological studies. As tremendous variations exist between media used for ALI-cultured human airway epithelial cells, our study aimed to evaluate the impact of several media (BEGMTM, PneumaCultTM, "Half&Half" and "Clancy") on cell type distribution using single-cell RNA sequencing and imaging. Our work revealed the impact of these media on cell composition, gene expression profile, cell signaling and epithelial morphology. We found higher proportions of multiciliated cells in PneumaCultTM-ALI and Half&Half, stronger EGF signaling from basal cells in BEGMTM-ALI, differential expression of the SARS-CoV-2 entry factor ACE2, and distinct secretome transcripts depending on media used. We also established that proliferation in PneumaCultTM-Ex Plus favored secretory cell fate, showing the key influence of proliferation media on late differentiation epithelial characteristics. Altogether, our data offer a comprehensive repertoire for evaluating the effects of culture conditions on airway epithelial differentiation and will help to choose the most relevant medium according to the processes to be investigated such as cilia, mucus biology or viral infection. We detail useful parameters that should be explored to document airway epithelial cell fate and morphology.

cell biology↗

bioRxiv2023

Early transcriptional similarities between two distinct neural lineages during ascidian embryogenesis

In chordates, the central nervous system arises from precursors that have distinct developmental and transcriptional trajectories. Anterior nervous systems are ontogenically associated with ectodermal lineages while posterior nervous systems are associated with mesoderm. Taking advantage of the well-documented cell lineage of ascidian embryos, we asked how the transcriptional states of the different neural lineages become similar during the course of progressive lineage restriction. We performed single-cell RNA sequencing (scRNA-seq) analyses on hand-dissected neural precursor cells of the two distinct lineages, together with those of their sister cell lineages, with a high temporal resolution covering five successive cell cycles from the 16-cell to neural plate stages. A transcription factor binding site enrichment analysis of neural specific genes at the neural plate stage revealed limited evidence for shared transcriptional control between the two neural lineages, consistent with their different ontogenies. Nevertheless, PCA analysis and hierarchical clustering showed that, by neural plate stages, the two neural lineages cluster together. Consistent with this, we identified a set of genes enriched in both neural lineages at the neural plate stage, including miR-124, CELF3/5/6, Zic.r-b, and Ets1/2.

developmental biology↗

bioRxiv2023

Lung injury shifts pulmonary capillary endothelial cells towards regeneration-associated Lrg1+ subpopulations with delayed dynamics in aged mice

Aging increases the risk of developing fibrotic diseases by hampering tissue regeneration after injury. Using longitudinal single-cell RNA-seq and spatial transcriptomics, here we compare the transcriptome of bleomycin-induced fibrotic lungs of young and aged mice, at 3 time points corresponding to the peak of fibrosis, regeneration and resolution. We find that lung injury shifts the transcriptomic profiles of three pulmonary capillary endothelial cells (PCEC) subpopulations. The associated signatures are linked to pro-angiogenic signaling with strong Lrg1 expression and do not progress similarly throughout the resolution process between young and old animals. Moreover, part of this set of resolution-associated markers is also detected in PCEC from samples of patients with idiopathic pulmonary fibrosis. Finally, we find that aging also alters the transcriptome of PCEC which display typical pro-fibrotic and pro-inflammatory features. We propose that age-associated alterations in specific PCEC subpopulations may interfere with the process of lung progenitor differentiation, thus contributing to the persistent fibrotic process typical of human pathology.

pathology↗

bioRxiv2022

An integrated cell atlas of the human lung in health and disease

Organ- and body-scale cell atlases have the potential to transform our understanding of human biology. To capture the variability present in the population, these atlases must include diverse demographics such as age and ethnicity from both healthy and diseased individuals. The growth in both size and number of single-cell datasets, combined with recent advances in computational techniques, for the first time makes it possible to generate such comprehensive large-scale atlases through integration of multiple datasets. Here, we present the integrated Human Lung Cell Atlas (HLCA) combining 46 datasets of the human respiratory system into a single atlas spanning over 2.2 million cells from 444 individuals across health and disease. The HLCA contains a consensus re-annotation of published and newly generated datasets, resolving under- or misannotation of 59% of cells in the original datasets. The HLCA enables recovery of rare cell types, provides consensus marker genes for each cell type, and uncovers gene modules associated with demographic covariates and anatomical location within the respiratory system. To facilitate the use of the HLCA as a reference for single-cell lung research and allow rapid analysis of new data, we provide an interactive web portal to project datasets onto the HLCA. Finally, we demonstrate the value of the HLCA reference for interpreting disease-associated changes. Thus, the HLCA outlines a roadmap for the development and use of organ-scale cell atlases within the Human Cell Atlas.

cell biology↗

bioRxiv2019

A single-cell atlas of the human healthy airways

RationaleThe respiratory tract constitutes an elaborated line of defense based on a unique cellular ecosystem. Single-cell profiling methods enable the investigation of cell population distributions and transcriptional changes along the airways. MethodsWe have explored cellular heterogeneity of the human airway epithelium in 10 healthy living volunteers by single-cell RNA profiling. 77,969 cells were collected by bronchoscopy at 35 distinct locations, from the nose to the 12th division of the airway tree. ResultsThe resulting atlas is composed of a high percentage of epithelial cells (89.1%), but also immune (6.2%) and stromal (4.7%) cells with peculiar cellular proportions in different sites of the airways. It reveals differential gene expression between identical cell types (suprabasal, secretory, and multiciliated cells) from the nose (MUC4, PI3, SIX3) and tracheobronchial (SCGB1A1, TFF3) airways. By contrast, cell-type specific gene expression was stable across all tracheobronchial samples. Our atlas improves the description of ionocytes, pulmonary neuro-endocrine (PNEC) and brush cells, which are likely derived from a common population of precursor cells. We also report a population of KRT13 positive cells with a high percentage of dividing cells which are reminiscent of "hillock" cells previously described in mouse. ConclusionsRobust characterization of this unprecedented large single-cell cohort establishes an important resource for future investigations. The precise description of the continuum existing from nasal epithelium to successive divisions of lung airways and the stable gene expression profile of these regions better defines conditions under which relevant tracheobronchial proxies of human respiratory diseases can be developed.

genomics↗

bioRxiv2018

Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration

BackgroundIt is usually considered that the upper airway epithelium is composed of multiciliated, goblet, secretory and basal cells, which collectively constitute an efficient first line of defense against inhalation of noxious substances. Upon injury, regeneration of this epithelium through proliferation and differentiation can restore a proper mucociliary function. However, in chronic airway diseases, the injured epithelium frequently displays defective repair leading to tissue remodeling, characterized by a loss of multiciliated cells and mucus hyper-secretion. Delineating drivers of differentiation dynamics and cell fate in the human airway epithelium is important to preserve homeostasis.\n\nResultsWe have used single cell transcriptomics to characterize the sequence of cellular and molecular processes taking place during human airway epithelium regeneration. We have characterized airway subpopulations with high resolution and lineage inference algorithms have unraveled cell trajectories from basal to luminal cells, providing markers for specific cell populations, such as deuterosomal cells, i.e. precursors of multiciliated cells. We report that goblet cells, like secretory cells, can act as precursors of multiciliated cells. Our study provides a repertoire of molecules involved in key steps of the regeneration process, either keratins or components of the Notch, Wnt or BMP/TGF{beta} signaling pathways. Our findings were confirmed in independent experiments performed on fresh human and pig airway samples, and on mouse tracheal epithelial cells.\n\nConclusionsOur single-cell RNA-seq study provides novel insights about airway epithelium differentiation dynamics, clarifies cell trajectories between secretory, goblet and multiciliated cells, identifies novel cell subpopulations, and maps the activation and repression of key signaling pathways.

cell biology↗

bioRxiv2018

Multiple independent adaptations to different ranges of host plants indicate high adaptability despite clonal reproduction in the nematode pest Meloidogyne incognita

The most devastating nematodes to worldwide agriculture are the root-knot nematodes with Meloidogyne incognita being the most widely distributed and damaging species. This parasitic and ecological success seem surprising given its supposed obligatory clonal reproduction. Clonal reproduction has been suspected based on cytological observations but, so far, never confirmed by population genomics data. At the species level, M. incognita is highly polyphagous with thousands of host plants. However, the host range varies among different M. incognita isolates that may present distinct and more restricted host compatibilities. Historically, four host races had been defined as a function of ranges of compatible and incompatible plants. We sequenced the genomes of 11 isolates across Brazil, covering these four distinct races to assess (i) how clonal reproduction is and (ii) how the level of genome variability associates with biological traits such as the host races, affected agronomic culture, and geographical distribution. By aligning the genomic reads of the isolates to the M. incognita reference genome assembly, we identified SNV and small-scale insertions/deletions. Analysis of linkage disequilibrium and 4-gametes test, showed no sign of recombination, confirming the clonal mode of reproduction of M. incognita. We showed that there are relatively few point variations between the different isolates, and these variations show no significant association with either the host races, the geographical origin of the samples or the host plant on which they have been collected. Due to the lack of phylogenetic signal underlying their existence, we recommend the discontinuation of the terminology race. Overall, these results suggest that multiple gains and losses of parasitic abilities and adaptations to different environmental conditions account for the broad host spectrum and wide geographic distribution of M. incognita. Hence, this nematode constitutes a model species to study adaptability without sexual recombination and overall low genomic variations in animals.

evolutionary biology↗