干细胞通过积累不同的表观遗传记忆来扩大潜力并改变组织适应性。
Stem cells expand potency and alter tissue fitness by accumulating diverse epigenetic memories.
机构信息
Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Immunology Discovery, Genentech Inc., South San Francisco, CA 94080, USA.
出版信息
Science. 2021 Nov 26;374(6571):eabh2444. doi: 10.1126/science.abh2444.
Immune and tissue stem cells retain an epigenetic memory of inflammation that intensifies sensitivity to future encounters. We investigated whether and to what consequence stem cells possess and accumulate memories of diverse experiences. Monitoring a choreographed response to wounds, we found that as hair follicle stem cells leave their niche, migrate to repair damaged epidermis, and take up long-term foreign residence there, they accumulate long-lasting epigenetic memories of each experience, culminating in post-repair epigenetic adaptations that sustain the epidermal transcriptional program and surface barrier. Each memory is distinct, separable, and has its own physiological impact, collectively endowing these stem cells with heightened regenerative ability to heal wounds and broadening their tissue-regenerating tasks relative to their naïve counterparts.
免疫细胞和组织干细胞保留着炎症的表观遗传记忆，这会增强它们对未来遭遇的敏感性。我们研究了干细胞是否具有并积累了不同经历的记忆，如果有，会产生什么后果。通过监测对创伤的协调反应，我们发现，当毛囊干细胞离开其龛位，迁移到受损的表皮处进行修复，并在那里长期定居时，它们会积累每次经历的持久的表观遗传记忆，最终导致修复后的表观遗传适应，维持表皮转录程序和表面屏障。每个记忆都是独特的、可分离的，并且具有自己的生理影响，这些记忆共同赋予了这些干细胞更强的再生能力来愈合伤口，并相对于它们的原始细胞扩大了它们的组织再生任务。
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