In certain highly regenerative animals, cellular dedifferentiation occurs after injury, allowing specialized cells to become progenitor cells for regeneration. However, this capacity is restricted in human cells due to reduced plasticity. Here, we introduce a chemical-induced dedifferentiation approach that reverts the differentiated cells to a progenitor-like state, conferring the features of human limb bud cells from human adult somatic cells. These chemically induced human limb-bud-like progenitors (hCiLBP cells) show a high degree of transcriptomic similarity to human embryonic limb bud progenitors. Importantly, we established culture conditions that allow hCiLBP cells to undergo extensive expansion while maintaining population homogeneity and long-term self-renewal capacity. Moreover, hCiLBP cells exhibit increased osteochondrogenic differentiation ability, providing an innovative platform for generation of skeletal lineage cell types. These results highlight a potential therapeutic approach for repairing damaged human tissues through reversal of developmental pathways from mature cells to expandable progenitor cells.

中文翻译：

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通过化学诱导的去分化产生人类可膨胀的肢芽样祖细胞


在某些高度再生的动物中，细胞去分化发生在受伤后，使特化细胞成为再生的祖细胞。然而，由于可塑性降低，这种能力在人类细胞中受到限制。在这里，我们介绍了一种化学诱导的去分化方法，该方法将分化的细胞恢复到祖细胞样状态，从而赋予了人类成年体细胞的肢芽细胞特征。这些化学诱导的人肢芽样祖细胞 （hCiLBP 细胞） 与人胚胎肢芽祖细胞表现出高度的转录组相似性。重要的是，我们建立了允许 hCiLBP 细胞进行广泛扩增的培养条件，同时保持群体均一性和长期自我更新能力。此外，hCiLBP 细胞表现出增强的骨软骨形成分化能力，为骨骼谱系细胞类型的生成提供了创新平台。这些结果突出了一种潜在的治疗方法，通过逆转从成熟细胞到可扩增祖细胞的发育途径来修复受损的人体组织。