DOI：10.1038/nature14289 作者：Deyou Zheng & Elaine Fuchs
摘要 : 成年干细胞能够沿一个细胞系分化，并能暂时离开它们的原始小环境，同时保持其可塑性。在这项研究中，Elaine Fuchs及同事在细胞系发展过程中和在干细胞处于它们小环境之外、暴露于一个新环境时两种情况下，对小鼠毛囊干细胞中的超级增强子和染色质动态进行了活体分析。
成年干细胞能够沿一个细胞系分化，并能暂时离开它们的原始小环境，同时保持其可塑性。在这项研究中，Elaine Fuchs及同事在细胞系发展过程中和在干细胞处于它们小环境之外、暴露于一个新环境时两种情况下，对小鼠毛囊干细胞中的超级增强子和染色质动态进行了活体分析。先驱因子(pioneer factor) SOX9 (直接与凝聚染色质结合的一种转录因子)被发现在促进和维持细胞命运中是毛囊干细胞的超级增强子的一个关键调控因子。
Adult stem cells occur in niches that balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, stem cells outside their niche often display fate flexibility1, 2, 3, 4. Here we show that super-enhancers5 underlie the identity, lineage commitment and plasticity of adult stem cells in vivo. Using hair follicle as a model, we map the global chromatin domains of hair follicle stem cells and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters (‘epicentres’) of transcription factor binding sites undergo remodelling upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicentres, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, hair follicle stem cells dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicentres, enabling their genes to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation.
来源： Nature 浏览次数：2