Generation of Human Expandable Limb Bud Cells via Chemically Induced Dedifferentiation Strategy [scRNA-seq]

Here, we introduce a novel chemically induced dedifferentiation approach that reverses the cellular development from a differentiated state to progenitor state with reduced senescence features, conferring the generation of limb bud progenitors from human adult mesenchymal stromal cells and dermal fibroblasts. These chemically induced limb bud cells (hCiLB cells) show a high degree of transcriptomic similarity to human embryonic limb bud cells. We found that hCiLB cells can undergo extensive expansion, while maintaining population homogeneity and long-term self-renewal capacity. Moreover, hCiLB cells exhibit increased osteochondrogenic differentiation ability than their parental cells, providing a new platform for the development of authentic articular cartilage. These results also highlight a potential therapeutic approach for the repair of damaged human tissues through reversal of developmental pathways from mature cells to expandable progenitor cells. Overall design: we use small-molecule combiantions to induce the dedifferentiation of human somatic cells to progenitors and then characterized the features of the progenitors.