Department of Biosciences and Nutrition and Center for Innovative Medicine, Karolinska Institutet, 14183 Huddinge, Sweden.
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
Cell Rep. 2018 Oct 16;25(3):585-597.e7. doi: 10.1016/j.celrep.2018.09.059.
Epithelial tissues, such as the skin, rely on cellular plasticity of stem cells (SCs) from different niches to restore tissue function after injury. How these molecularly and functionally diverse SC populations respond to injury remains elusive. Here, we genetically labeled Lgr5- or Lgr6-expressing cells from the hair follicle bulge and interfollicular epidermis (IFE), respectively, and monitored their individual transcriptional adaptations during wound healing using single-cell transcriptomics. Both Lgr5 and Lgr6 progeny rapidly induced a genetic wound signature that, for Lgr5 progeny, included the remodeling of receptors to permit interactions with the wound environment, a property that Lgr6 progeny possessed even before wounding. When contributing to re-epithelialization, Lgr5 progeny gradually replaced their bulge identity with an IFE identity, and this process started already before Lgr5 progeny left the bulge. Altogether, this study reveals how different SCs respond and adapt to a new environment, potentially explaining cellular plasticity of many epithelial tissues.
上皮组织（如皮肤）依赖于不同龛位的干细胞（SCs）的细胞可塑性，以在损伤后恢复组织功能。这些分子和功能上不同的 SC 群体如何响应损伤仍然难以捉摸。在这里，我们分别对毛囊隆突和毛囊间表皮（IFE）中的 Lgr5 或 Lgr6 表达细胞进行了遗传标记，并使用单细胞转录组学监测了它们在伤口愈合过程中的单个转录适应性。Lgr5 和 Lgr6 的后代都迅速诱导了一个遗传的伤口特征，对于 Lgr5 的后代来说，这个特征包括了受体的重塑，以允许与伤口环境相互作用，而 Lgr6 的后代甚至在受伤之前就已经具备了这种特性。当参与再上皮化时，Lgr5 的后代逐渐用 IFE 特性取代其隆突特性，而且这个过程早在 Lgr5 的后代离开隆突之前就已经开始了。总的来说，这项研究揭示了不同的 SC 如何响应和适应新的环境，这可能解释了许多上皮组织的细胞可塑性。
