Program in Craniofacial Biology and Department of Orofacial Sciences, University of California, San Francisco, CA, USA.
Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Nat Cell Biol. 2019 Sep;21(9):1102-1112. doi: 10.1038/s41556-019-0378-2. Epub 2019 Sep 2.
The classical model of tissue renewal posits that small numbers of quiescent stem cells (SCs) give rise to proliferating transit-amplifying cells before terminal differentiation. However, many organs house pools of SCs with proliferative and differentiation potentials that diverge from this template. Resolving SC identity and organization is therefore central to understanding tissue renewal. Here, using a combination of single-cell RNA sequencing (scRNA-seq), mouse genetics and tissue injury approaches, we uncover cellular hierarchies and mechanisms that underlie the maintenance and repair of the continuously growing mouse incisor. Our results reveal that, during homeostasis, a group of actively cycling epithelial progenitors generates enamel-producing ameloblasts and adjacent layers of non-ameloblast cells. After injury, tissue repair was achieved through transient increases in progenitor-cell proliferation and through direct conversion of Notch1-expressing cells to ameloblasts. We elucidate epithelial SC identity, position and function, providing a mechanistic basis for the homeostasis and repair of a fast-turnover ectodermal appendage.
经典的组织更新模型假设,在终末分化之前,少量静止的干细胞(SCs)通过增殖产生过渡扩增细胞。然而,许多器官中存在着具有增殖和分化潜能的干细胞池,这些潜能与这一模板不同。因此,解析干细胞的特性和组织是理解组织更新的核心。在这里,我们结合单细胞 RNA 测序(scRNA-seq)、小鼠遗传学和组织损伤方法,揭示了维持和修复不断生长的小鼠门齿的细胞层次结构和机制。我们的结果表明,在体内平衡状态下,一群活跃循环的上皮祖细胞产生产生釉质的成釉细胞和相邻的非成釉细胞层。损伤后,组织修复是通过祖细胞增殖的短暂增加和 Notch1 表达细胞的直接转化为成釉细胞来实现的。我们阐明了上皮干细胞的特性、位置和功能,为快速周转的外胚层附属物的体内平衡和修复提供了机制基础。
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