Single-cell RNA Sequencing Resolves Spatiotemporal Development of Pre-thymic Lymphoid Progenitors and Thymus Organogenesis in Human Embryos

Human T lymphogenesis includes emergence, migration and thymus-seeding of T lymphoid precursor, followed by T-lymphocytes commitment in thymus, which are largely unknown. Here, we perform single-cell RNA sequencing using cells isolated from human hemogenic/hematopoietic sites such as aorto-gonad-mesonephros (AGM), liver, and thymic primordia spanning embryonic and fetal stages. The transcriptional atlas of thymic primordia illustrates the cellular trajectory of early T-lymphocyte development. Further, thymic seeding progenitors in liver and unique T lymphoid progenitors in AGM at CS14, are first unveiled. We also reveal the stepwise-specification of thymic epithelial cells,and the potential cell-cell interactions between T-lymphocyte progenitors and stromal cells during thymus organogenesis. Our data provide new insights into T lymphogenesis, which prospectively directs the efficient regeneration of T- lymphocytes from pluripotent stem cells Overall design: Here, we performed single-cell RNA sequencing (RNA-Seq) analysis of about 26,000 individual cells from four organs and tissues of CS14 to week 10 of gestation in human embryos/fetus, including thymus, AGM region, liver and blood