Maturation exploration of kidney organoids from single-cell RNA-seq data analysis
Résumé
Organoids are complex 3D structures derived from stem cells. They display architectures and functionalities similar to in vivo organs. Organ-specific studies were able to confirm the structure and the composition of mature organoids by comparing cell populations found in organoids with the ones found in the target organ. This comparison is possible by analyzing singe-cell RNA-seq data of organoids to identify cell populations. In this context, we wanted to explore these sequencing data from organoids at different times of culture and observe, without a priori, their maturation by using descriptive and statistical methods.
We investigated single-cell RNA-seq public datasets of kidney organoids at different days of maturations from 2 different commercial cell lines (Subramanian et al, Nature communication, 2019). We integrated the datasets from the different maturation days to highlight cell specificities for each stage of maturation. We also studied cell trajectories to observe correlations between cell differentiation and the date of maturation. We finally used statistical methods to explore the variability of cell proportions between days of maturations.
From this preliminary study, computational analyses could defined 2 distinct early and late maturation levels in kidney organoids.
The perspectives of this project is to continue the maturation exploration on different datasets and possibly on organoids of other target organs. The final objective is to use machine-learning-based approaches to develop a computational method that can estimate the maturation level of organoids.
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