Molecular architecture of mesoderm cells across early to middle stage of human embryo development at single-cell resolution

Abstract Background The differentiation of mesodermal cells (MCs) in the early stage of embryonic development contributes to the organogenesis of several core organs. However, the single-cell molecular architecture of MCs and the key molecular events during the differentiation remain unclear. Methods We performed single-cell RNA sequencing (RNA sequencing) and single-cell assay for transposase-accessible chromatin (ATAC-Seq) to analyze the developmental features of MCs to heart, kidney, spleen, liver, and brain in human embryos at gestational ages 7–17 weeks. Results We found that EGR1 might be relevant to the differentiation of heterogeneous MC sub-clusters. Meanwhile, RPL10P9+PTMAP5+ MCs had the closest expression profiling with endocardial cells. NDUFA4L2+A2M+ MCs presented the potentials to form endothelial cells (ECs) and hematopoietic stem cells, and MEF2C might be involved in this process. Conclusions These findings provide insights into the molecular architecture and lineage progression of MCs during early human embryonic organogenesis, offering a valuable reference for regenerative medicine and organ bioengineering.