PhD Thesis (M/F) Human neural stem cell lineages

Laboratory

 The Baffet lab is located at Institut Curie, in the department of cell biology (UMR144). http://institut-curie.org/team/baffet.

The team investigates the mechanisms of mammalian neocortex development, with a strong focus on neural stem cells. We aim to understand how these cells shape the cel type diversity of the brain, using live imaging-based approaches.

 Description of the PhD thesis project

The remarkable expansion of the human neocortex during recent primate evolution is thought to result from increased production of neuronal and glial cells by neural stem cells, known as radial glial (RG) cells. However, the cell fate decisions that generate this diversity, and how they vary across developmental stages and cortical regions, remain poorly understood. This PhD project aims to uncover the lineage relationships and fate decisions of human neural stem cells across cortical regions using a combination of human fetal tissue and next-generation regionalized cortical organoids developed within an ERC Synergy project. Building on a live/fixed correlative imaging pipeline established in the host laboratory, the student will directly observe RG cell divisions and assign the identities of their progeny through immunostaining. By quantifying proliferative, neurogenic, and gliogenic division modes across space and time, they will generate a comprehensive map of neural stem cell fate decisions during human cortical development and determine how these programs vary between cortical areas. To investigate the molecular mechanisms underlying these fate choices, they will combine single-cell transcriptomics with lineage analysis. Using Live-seq, a minimally invasive approach that enables transcriptome profiling of living cells, they will sample individual RG cells in 2D prior to division and subsequently determine the identity of their daughter cells through live/fixed correlative imaging. This strategy will establish direct links between the molecular state of neural stem cells and their developmental output, allowing us to identify transcriptional signatures associated with specific fate decisions and test whether RG cells are molecularly precommitted to fate decisions before mitosis. Together, this work will provide an unprecedented spatiotemporal map of human neural stem cell lineages, reveal the molecular determinants of fate specification, and establish new principles governing regional diversification of the developing human cortex.