The study aimed to describe developmental trajectories of thymocytes and mature T cells using a new tool called tviblindi. tviblindi is a modular trajectory inference algorithm that integrates pseudotime inference, random walk simulations, real-time topological classification using persistent homology, and autoencoder-based 2D visualization.
The key highlights and insights from the study are:
tviblindi offers a highly scalable, linear complexity framework that works at the single-cell level and avoids artifacts of dimensionality reduction. It allows the user to interactively explore the data and set the appropriate level of resolution.
When applied to mass cytometry data of human thymocytes and peripheral blood T cells, tviblindi was able to reconstruct the known sequence of T-cell maturation steps, from early progenitors to mature naive and effector T cells in the periphery.
tviblindi revealed a distinct trajectory leading to a population of thymic CD4+CD8dim cells, which were identified as recirculating mature regulatory T cells (Tregs). These cells express markers associated with activated and proliferating Tregs, and likely home back to the thymus from the periphery.
The study provides a detailed characterization of thymic Treg development, tracing their progression from the negative selection stage to mature thymic Tregs with an extensive proliferation history.
tviblindi is a versatile and generic approach suitable for any mass cytometry or single-cell RNA-seq dataset, equipping biologists with an effective tool for interpreting complex data on cell development and differentiation.
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by Stuchly,J., ... alle www.biorxiv.org 07-15-2023
https://www.biorxiv.org/content/10.1101/2023.07.13.547329v3Domande più approfondite