sc4DMap · Spatiotemporal analysis of mammalian embryonic development at single-cell level

Spatiotemporal analysis of mammalian embryonic development at single-cell level

Early mammalian embryonic development relies on precise, spatiotemporal regulation of gene expression at the single-cell level. Despite significant progress in developmental biology, it remains a fundamental challenge to understand how individual cell behaviors govern complex processes like gastrulation and organogenesis in these early stages. A key knowledge gap persists in linking the dynamic movements of cells with their gene expression states throughout development. Recent advances in two complementary technologies—spatial transcriptomics at the single-cell level and in toto imaging—provide powerful tools to explore this gap. Spatial transcriptomics enables the examination of gene expression in specific locations within tissues, while in toto imaging captures the dynamic behavior of cells as they transition from single-cell stages to fully formed organisms. However, these techniques have not yet been combined at scale in more complex mammalian systems, a limitation that has hindered a more comprehensive understanding of early developmental processes. This project aims to address this challenge by integrating spatial transcriptomics with in toto imaging to investigate early mammalian development. For the first time, real-time tracking of cellular dynamics will be linked with spatiotemporal gene expression profiles across the developing embryo, offering unprecedented insights into how cells move, interact, and regulate their own gene expression. This integrative approach will allow us to map cellular behaviors and their associated gene expression patterns, ultimately revealing the mechanisms that determine cell fate. The core objective is to develop a novel framework for the integration of these two technologies, resulting in the first cellular-resolution, four-dimensional gene expression map of mammalian embryo development. This map will reflect both cellular dynamics and gene expression at the single-cell level, providing a foundational resource for future studies. In the longer term, this work will set the stage for the broader integration of multi-omics approaches, which have been increasingly explored in single-cell studies but remain underdeveloped in dynamic, multi-cellular contexts. By advancing our understanding of early embryonic development, this project will provide valuable insights into fundamental biological processes and offer new perspectives on how cell fate is determined in mammalian systems.

Data: CORDIS, © European Union