Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Princess Máxima Center for Pediatric Oncology and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands; email:
Centre for Stem Cells and Regenerative Medicine, King's College London, London SE1 9RT, United Kingdom; email:
Annu Rev Biochem. 2018 Jun 20;87:1015-1027. doi: 10.1146/annurev-biochem-062917-012341. Epub 2018 Mar 1.
Central to the classical hematopoietic stem cell (HSC) paradigm is the concept that the maintenance of blood cell numbers is exclusively executed by a discrete physical entity: the transplantable HSC. The HSC paradigm has served as a stereotypic template in stem cell biology, yet the search for rare, hardwired professional stem cells has remained futile in most other tissues. In a more open approach, the focus on the search for stem cells as a physical entity may need to be replaced by the search for stem cell function, operationally defined as the ability of an organ to replace lost cells. The nature of such a cell may be different under steady state conditions and during tissue repair. We discuss emerging examples including the renewal strategies of the skin, gut epithelium, liver, lung, and mammary gland in comparison with those of the hematopoietic system. While certain key housekeeping and developmental signaling pathways are shared between different stem cell systems, there may be no general, deeper principles underlying the renewal mechanisms of the various individual tissues.
经典的造血干细胞（HSC）范式的核心概念是，血细胞数量的维持完全由一个离散的物理实体来执行：可移植的 HSC。HSC 范式一直是干细胞生物学中的典型模板，但在大多数其他组织中，对稀有、固定专业干细胞的寻找仍然徒劳无功。在一种更为开放的方法中，对作为物理实体的干细胞的寻找可能需要被对干细胞功能的寻找所取代，这种功能被操作性地定义为器官替换丢失细胞的能力。在稳态条件和组织修复期间，这种细胞的性质可能会有所不同。我们讨论了一些新兴的例子，包括皮肤、肠道上皮、肝脏、肺和乳腺的更新策略，以及与造血系统的比较。虽然不同的干细胞系统之间共享某些关键的管家和发育信号通路，但各种单个组织的更新机制可能没有普遍的、更深层次的原则。
