Mots-Clés
spatial transcriptomics
medulloblastoma
3D reconstruction
computational frameworks
Description
About Cell-ID
The Cell-ID program focuses on uncovering the molecular mechanisms that govern cell fate determination during neural development and how their disruption contributes to childhood brain cancers.
Our goal is to design strategies for a cell-based interceptive medicine: targeting the earliest cellular and molecular events in cancer to prevent disease progression.
Led by CNRS and Inserm, in collaboration with major French institutions and international partners, Cell-ID integrates omics technologies, advanced imaging, and computational modeling to study genome function and 3D nuclear organization in neural tissues under normal and pathological conditions. By combining cutting-edge experimental tools with predictive models, the program aims to define and modulate cell trajectories during neural development.
About this project
Long-Read Single-Cell and Spatial Transcriptomics of the Developing Human Hindbrain
Pascal Barbry and Alain Chédotal
This proposal aims to characterize human hindbrain (Cerebellum and brainstem) development using an integrated pipeline combining long-read nanopore sequencing (ScNaUmi-seq and SiT) with spatial transcriptomics, to better understand the cellular origins of medulloblastoma. We will shift from gene-centric to transcript-centric paradigms by capturing full-length sequence heterogeneity and splicing diversity lost in standard workflows. Our experimental approach combines single-nuclei/single-cell RNA sequencing with dual spatial methods: SiT for global isoform mapping and Xenium for precise cell-cell interaction analysis on adjacent tissue sections. Targeted in situ sequencing will generate spatial maps enabling probabilistic cell mapping and 3D reconstruction from optically cleared specimens or tissue section processed with multiplex immunostaining. We will develop AI-driven computational frameworks for multi-omics integration and annotation, incorporating Human Cell Atlas resources.
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Methods will be optimized for rare embryonic samples to capture long transcripts. Using unique access to human embryonic tissue, we will map neuronal progenitor lineages and their spatial organization during brainstem development. By establishing a comprehensive developmental atlas, we aim to identify the progenitor populations susceptible to malignant transformation in medulloblastoma, the most common pediatric brain cancer with no cure to date.
This project is a direct collaboration between the team of Pascal Barbry (Nice) and Alain Chédotal (Institut de la Vision Paris et MeLIS, Lyon) who will co-supervise the student. The student will be mainly located in Paris but will visit regularly the Barbry lab. This project is part of a national effort to characterize cell derailment in pediatric brain cancer via the consortium Cell-ID.