近日，北京大学邓宏魁等研究人员合作，通过化学诱导去分化生成可扩展的人类肢芽样祖细胞。相关论文于2024年10月22日在线发表在《细胞—干细胞》杂志上。

研究人员介绍了一种化学诱导去分化的方法，能够将分化细胞逆转为祖细胞样状态，从人类成年体细胞中赋予人类肢芽细胞的特征。这些化学诱导的人类肢芽样祖细胞（hCiLBP细胞）与人类胚胎肢芽祖细胞具有高度的转录组相似性。

重要的是，研究人员建立了培养条件，使hCiLBP细胞能够在维持群体均一性和长期自我更新能力的同时，进行广泛扩增。此外，hCiLBP细胞表现出增强的骨软骨分化能力，为骨骼谱系细胞类型的生成提供了创新平台。

这些结果突显了一种潜在的治疗方法，通过将成熟细胞的发育通路逆转为可扩展的祖细胞，以修复受损的人类组织。

研究人员表示，在某些高度再生的动物中，细胞去分化在损伤后发生，使得专门化细胞能够转变为再生的祖细胞。然而，这种能力在人类细胞中因可塑性降低而受到限制。

附：英文原文

Title: Generation of human expandable limb-bud-like progenitors via chemically induced dedifferentiation

Author: Jialiang Zhu, Xinxing Zhong, Huanjing He, Jingxiao Cao, Zhengyang Zhou, Jiebin Dong, Honggang Li, Anqi Zhang, Yulin Lyu, Cheng Li, Jingyang Guan, Hongkui Deng

Issue&Volume: 2024-10-22

Abstract: 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.

DOI: 10.1016/j.stem.2024.10.001

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00363-1