Production of live monkeys and their genetically matched embryonic stem cells from single embryos

Immune rejection poses a challenge in stem cell therapy, especially with allogeneic embryonic stem cells (ESCs). Non-human primates offer a promising avenue for developing genetically matched ESCs for regenerative medicine. Here, we successfully derive three live monkeys and their genetically matched autologous ESCs (aESCs) using embryo splitting. Additionally, from fibroblasts of one of these monkeys, we generate induced pluripotent stem cells (iPSCs) and nuclear transfer embryonic stem cells (ntESCs), creating a set of genetically matched aESCs, iPSCs, and ntESCs. Single-cell RNA-seq analysis reveals that aESCs potentially exhibit reduced heterogeneity, lower transcriptional noise, and enhanced genomic stability compared to iPSCs and ntESCs. Furthermore, we successfully derive ESCs from human split embryos, highlighting the potential for obtaining human aESCs. Collectively, our study offers an avenue for establishing autologous pluripotent stem cells and provides the theoretical basis as well as research model for further application of aESCs in human regenerative medicine.