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

Here, we introduce a novel chemically induced dedifferentiation approach that reverses the cellular development from a differentiated state to progenitor state, 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.