Biology subjects

Viel, R.

Publications and source records attributed to Viel, R..

4 recordsLinked to original sources

bioRxiv2026

An internal scaffold supports microtubule architectural diversity in Xenopus spermatids

During spermiogenesis, early round spermatids differentiate into specialized spermatozoa through an extensive reshaping of the nucleus driven by coordinated cytoskeletal and chromatin-based mechanisms. In mammals, this process critically relies on the transient manchette, a microtubule-based structure that remodels the spermatid nucleus and serves a track to transport material required for flagellum assembly. However, the existence, organization, and molecular composition of such a structure in other vertebrates have remained poorly investigated. Here, we establish that an organized microtubule network is present in Xenopus spermatids and shares key architectural and molecular hallmarks of the mammalian manchette. We further uncover a large structural heterogeneity of spermatid microtubules, with variable protofilament numbers, skew angles, and lattice organizations. We reveal the presence of a Spaca9-Saxo2 internal scaffold in spermatid microtubules suggesting an internal reinforcement mechanism necessary for extensive nuclear reshaping and cytoplasm remodeling.

cell biology↗

bioRxiv2024

Primary cilia promote EMT-induced triple-negative breast tumor heterogeneity and resistance to therapy

Tumor heterogeneity and plasticity, driven by Epithelial-Mesenchymal Transition (EMT), enable cancer therapeutic resistance. We previously showed that EMT promotes primary cilia formation, which enables stemness and tumorigenesis in triple-negative breast cancer (TNBC). Here, we establish a role for primary cilia in human TNBC chemotherapeutic resistance. We developed patient-derived organoids, and showed that these recapitulated the cellular heterogeneity of TNBC biopsies. Notably, one of the identified cell states bore a quasi-mesenchymal phenotype, primary cilia, and stemness signatures. We treated our TNBC organoids with chemotherapeutics and observed partial killing. The surviving cells with organoid-reconstituting capacity showed selective enrichment for the quasi-mesenchymal ciliated cell subpopulation. Genomic analyses argue that this enrichment reflects a combination of pre-existing cells and ones that arose through drug-induced cellular plasticity. We developed a family of small-molecule inhibitors of ciliogenesis and show that these, or genetic ablation of primary cilia, suppress chemoresistance. We conclude that primary cilia help TNBC to evade chemotherapy. SignificanceCancer cells that activate EMT to acquire a quasi-mesenchymal state form primary cilia to evade chemotherapy in human triple-negative breast cancer. Pharmacological inhibition of primary ciliogenesis counteracts EMT-induced chemoresistance.

cancer biology↗

bioRxiv2023

Eye lens organoids going simple: characterization of a new 3-dimensional organoid model for lens development and pathology

The ocular lens, along with the cornea, focuses light on the retina to generate sharp images. Opacification of the lens, or cataract, is the leading cause of blindness worldwide. Presently, the best approach for cataract treatment is to surgically remove the diseased lens and replace it with an artificial implant. Although effective, this is costly and can have post-surgical complications. Toward identifying alternate treatments, it is imperative to develop organoid models relevant for lens studies and anti-cataract drug screening. Here, we demonstrate that by culturing mouse lens epithelial cells under defined 3-dimensional (3D) culture conditions, it is possible to generate organoids that display optical properties and recapitulate many aspects of lens organization at the tissue, cellular and transcriptomic levels. These 3D cultured lens organoids can be rapidly produced in large amounts. High-throughput RNA-sequencing (RNA-seq) on specific organoid regions isolated by laser capture microdissection (LCM) and immunofluorescence assays demonstrate that these lens organoids display spatiotemporal expression of key lens genes, e.g., Jag1, Pax6, Prox1, Hsf4 and Cryab. Further, these lens organoids are amenable to induction of opacities. Finally, knockdown of a cataract-linked RNA-binding protein encoding gene, Celf1, induces opacities in these organoids, indicating their use in rapidly screening for genes functionally relevant to lens biology and cataract. In sum, this lens organoid model represents a compelling new tool to advance the understanding of lens biology and pathology, and can find future use in the rapid screening of compounds aimed at preventing and/or treating cataract.

cell biology↗

bioRxiv2021

The mechanosensitive TRPV2 calcium channel controls melanoma invasiveness and metastatic potential.

Discovery of therapeutic targets against metastasis is of primary importance since being the main cause of cancer-related death. Melanoma is a highly aggressive cancer endowed with a unique capacity of rapidly metastasizing. Deregulation of calcium homeostasis has been involved in numerous cellular metastatic behaviors, although the molecular determinants supporting these processes often remain unclear. Here, we evidenced a prominent expression of the plasma membrane TRPV2 calcium channel as a distinctive feature of melanoma tumors, directly related to melanoma metastatic progression and dissemination. In vitro as well as in vivo, TRPV2 activity was sufficient to confer both migratory and invasive phenotypes to non-invasive melanoma cells, while conversely upon TRPV2 silencing, highly metastatic melanoma cells failed to retain their malignant behaviors. We established a model whereupon activation of the mechanosensitive TRPV2 channel, localized in highly dynamic nascent adhesion clusters, directly regulates calpain-dependent cleavage of the adhesive protein talin together with F-actin network. By operating at the crossroad of the tumor microenvironment and the intracellular machinery, mechanosensitive TRPV2 channel controls melanoma cells aggressiveness. Finally in human melanoma tumor samples, TRPV2 overexpression represents a molecular marker of advanced malignancy and bad prognosis, highlighting a new therapeutic option for migrastatics in the treatment of metastatic melanoma. SignificanceOne essential feature of metastatic cells is enhanced motility and invasiveness. This study evidences TRPV2 channel control over metastatic melanoma invasiveness, highlights new migration regulatory mechanisms, and reveals this channel as a biomarker and migrastatic target for the treatment of advanced melanoma.

cancer biology↗