Biology subjects

Vivie, J.

Publications and source records attributed to Vivie, J..

3 recordsLinked to original sources

bioRxiv2020

A genome-wide CRISPR/Cas phenotypic screen formodulators of DUX4 cytotoxicity reveals screen complications

Facioscapulohumeral muscular dystrophy (FHSD), a fundamentally complex muscle disorder that thus far remains untreatable. As the name implies, FSHD starts in the muscles of the face and shoulder gridle. The main perturbator of the disease is the pioneer transcription factor DUX4, which is misexpressed in affected tissues due to a failure in epigenetic repressive mechanisms. In pursuit of unraveling the underlying mechanism of FSHD and finding potential therapeutic targets or treatment options, we performed an exhaustive genome-wide CRISPR/Cas9 phenotypic rescue screen to identify modulators of DUX4 cytotoxicity. We found no key effectors other than DUX4 itself, suggesting treatment efforts in FSHD should be directed towards its direct modulation. The screen did however reveal some rare and unexpected Cas9-induced genomic events, that may provide important considerations for planning future CRISPR/Cas9 knock-out screens.

molecular biology↗

bioRxiv2020

Human Prostate Cancer-Associated Macrophage Subtypes with Prognostic Potential Revealed by Single-cell Transcriptomics

Macrophages in the tumor microenvironment are causally linked with prostate cancer development and progression, yet little is known about their composition in neoplastic human tissue. By performing single cell transcriptomic analysis of human prostate cancer resident macrophages, three distinct populations were identified in the diseased prostate. Unexpectedly, macrophages isolated from the tumor-adjacent site of the prostatectomy specimen were identical to those from the tumorous site. Markers associated with canonical M1 and M2 macrophage phenotypes were identifiable, however these were not the main factors defining unique subtypes. The genes selectively associated with each macrophage cluster were used to develop a gene signature which was highly associated with both recurrence-free and metastasis-free survival. These results highlight the relevance of tissue-specific macrophage subtypes in the tumour microenvironment for prostate cancer progression and demonstrates the utility of profiling single-cell transcriptomics in human tumor samples as a strategy to design gene classifiers for patient prognostication.

immunology↗

bioRxiv2019

Polar-like trophoblast stem cells form an embryonic-abembryonic axis in blastoids.

The early mammalian conceptus (blastocyst) comprises an outer trophoblast globe that forms an axis originating from the inner embryonic cells. From the mouse conceptus, Trophoblast stem cells (TSCs) are derived, which are in vitro analogues of early trophoblasts. Here, we show that TSCs contain plastic subpopulations reflecting developmental states ranging from pre- to post-implantation trophoblasts. However, upon exposure to a specific combination of embryonic inductive signals, TSCs globally acquire properties of pre-implantation polar trophoblasts (gene expression, self-renewal) juxtaposing the inner embryonic cells, and an enhanced, homogeneous epithelial phenotype. These lines of polar-like TSCs (pTSCs) represent a transcriptionally earlier state that more efficiently forms blastoids, whose inner embryonic cells then induce the patterning of gene expression along the embryonic-abembryonic axis. Altogether, delineating the requirements and properties of polar trophoblasts and blastocyst axis formation in vitro provides a foundation for the precise description and dissection of early development.

developmental biology↗