SRA

The behavior of (stem) cells is regulated by their local microenvironment through biochemical and biophysical interactions. To advance our understanding of the molecular characteristics and key components of the microenvironment, we applied a genome-wide RNA tomography sequencing approach in zebrafish, chicken, mouse and human embryos. The resulting anterior-posterior and/or dorsal-ventral transcriptional maps provide a powerful resource for identifying and comparing expression patterns in a given tissue or microenvironment along the embryonic axes of multiple species. We used these maps to explore the regulatory function of the aortic microenvironment, where the first hematopoietic stem cells are generated during embryonic development. By performing inter-species comparative analyses, we identified and functionally validated new conserved regulators of hematopoietic stem cell generation. Further analysis of spatial transcriptomics will elucidate the regulatory functions of the local microenvironment in vivo, paving the way for improved (stem) cell production in vitro and clinical cell therapy. Overall design: Spatial transcriptomics by RNA-tomography (Tomo-seq) on whole or sub-dissected embryos (processed along the anterior-to-posterior axis) and on transversal thick slices (processed along the dorsal-to-ventral axis).