Single-cell and spatial genome-plus-transcriptome analyses to understand cellular heterogeneity and cell competition in embryogenesis

Currently, the understanding of transcriptional regulation and gene expression networks that empower early development is largely derived from single-cell RNA-sequencing analyses of pre-implantation embryos. However, these technologies are inherently limited by low sensitivity, technical noise and loss of crucial spatial information due to embryo dissociation prior to analyses. Furthermore, the first cell divisions of human life after fertilization are prone to chromosome instability (CIN), but its cause(s) and impact on development remain poorly understood. Near absolute RNA sensitivity technologies that in parallel can provide DNA and/or protein readouts of a single cell are needed to address important remaining questions on DNA copy-number driven perturbation of gene regulatory networks in the embryo as well as to identify causes of CIN. Additionally, retaining molecular as well as cellular spatial information is crucial to investigate gene expression perturbation in relation to CIN-distorted nuclear architecture, 'aneuploid cell – euploid cell' communication and processes of cell competition within the embryo. Hence, establishing innovative spatial transcriptomics methods based on sequential fluorescence in situ hybridization (seqFISH) technologies, and developing them for embryo research and multi-omics spatial assays are very important and necessary.