Zhu Jialiang, Zhong Xinxing, He Huanjing, Cao Jingxiao, Zhou Zhengyang, Dong Jiebin, Li Honggang, Zhang Anqi, Lyu Yulin, Li Cheng, Guan Jingyang, Deng Hongkui
MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences and MOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China; BeiCell Therapeutics, Beijing, China; BeiCell Therapeutics, Suzhou, China.
MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences and MOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China; State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
Cell Stem Cell. 2024 Dec 5;31(12):1732-1740.e6. doi: 10.1016/j.stem.2024.10.001. Epub 2024 Oct 22.
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.
在某些具有高度再生能力的动物中，细胞去分化在损伤后发生，使特化细胞成为用于再生的祖细胞。然而，由于可塑性降低，这种能力在人类细胞中受到限制。在此，我们引入一种化学诱导去分化方法，该方法可使分化细胞恢复到祖细胞样状态，赋予人类成体细胞以人类肢体芽细胞的特征。这些化学诱导的人类肢体芽样祖细胞（hCiLBP细胞）与人类胚胎肢体芽祖细胞表现出高度的转录组相似性。重要的是，我们建立了培养条件，使hCiLBP细胞能够进行广泛扩增，同时保持群体同质性和长期自我更新能力。此外，hCiLBP细胞表现出增强的成骨软骨分化能力，为生成骨骼谱系细胞类型提供了一个创新平台。这些结果凸显了一种潜在的治疗方法，即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。
