研究人员发现，如果不解决谱系的可塑性，皮肤干细胞就不能在体外有效地生成每一个谱系，也不能在体内再生毛发和修复受伤的表皮。通过小分子筛选，研究人员发现视黄酸是一个关键的调节因子。结合高通量方法、细胞培养和体内小鼠遗传学，研究人员剖析了视黄酸在组织再生中的作用。
研究人员发现，视黄酸是在毛囊干细胞微环境中局部制造的，其含量决定了毛囊干细胞的特性和用途。这些发现对毛发生长、慢性伤口和癌症都有治疗意义，因为这些疾病的细胞谱系可塑性尚未解决。
据介绍，谱系可塑性（一种双重命运表达状态）是将干细胞从其微环境限制中释放出来，并将其重新定向到最需要它们的组织区划所需的。
附：英文原文
Title: Vitamin A resolves lineage plasticity to orchestrate stem cell lineage choices
Author: Matthew T. Tierney, Lisa Polak, Yihao Yang, Merve Deniz Abdusselamoglu, Inwha Baek, Katherine S. Stewart, Elaine Fuchs
Issue&Volume: 2024-03-08
Abstract: Lineage plasticity—a state of dual fate expression—is required to release stem cells from their niche constraints and redirect them to tissue compartments where they are most needed. In this work, we found that without resolving lineage plasticity, skin stem cells cannot effectively generate each lineage in vitro nor regrow hair and repair wounded epidermis in vivo. A small-molecule screen unearthed retinoic acid as a critical regulator. Combining high-throughput approaches, cell culture, and in vivo mouse genetics, we dissected its roles in tissue regeneration. We found that retinoic acid is made locally in hair follicle stem cell niches, where its levels determine identity and usage. Our findings have therapeutic implications for hair growth as well as chronic wounds and cancers, where lineage plasticity is unresolved.
DOI: adi7342
Source: https://www.science.org/doi/10.1126/science.adi7342