Human stem cells with in vivo high plasticity generated by cell-cell communication

We report the discovery of a population of tiny, dormant cells from human peripheral blood, which upon activation and maturation in vitro exhibit unique transcriptome and cellular phenotypes, distinct from all known cell types. These novel cells can deliver RNA-rich granules to suitable recipient cells and provide guidance, and are thus named “mature Guide Cells” (or m-GCs) and their dormant precursors are named “pre-GCs.” When m-GCs are co-cultured with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs), cell-cell communication occurs in which RNA-rich granules are transferred from m-GCs to UC-MSCs via tunneling nanotubes (TNT). As a result, a novel type of stem cells with high plasticity is generated, which can be induced to differentiate into the representative cell types from all three germ layers in vitro. The newly generated stem cells, named “guide integrated adult Stem Cells” (or giaSCs) are characterized by unique cell morphology, gene expression, and phenotypic profile. They are also observed to have a remarkable capacity to promote tissue reconstitution in vivo. We conducted experiments to obtain RNA-seq data for human guide cells (pre-GC and m-GC), UC-MSC, and giaSC. For each of the cell type, we extracted RNA from 2 individuals as biological replicates, with 2-3 technical replicates per individual. Single cell RNA-seq data were also generated from m-GC.