Saxena Madhurima, Shivdasani Ramesh A
Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; email:
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts 02215, USA.
Annu Rev Physiol. 2021 Feb 10;83:405-427. doi: 10.1146/annurev-physiol-021119-034520. Epub 2020 Nov 24.
The cardinal properties of adult tissue stem cells are self-renewal and the ability to generate diverse resident cell types. The daily losses of terminally differentiated intestinal, skin, and blood cells require "professional" stem cells to produce replacements. This occurs by continuous expansion of stem cells and their immediate progeny, followed by coordinated activation of divergent transcriptional programs to generate stable cells with diverse functions. Other tissues turn over slowly, if at all, and vary widely in strategies for facultative stem cell activity or interconversion among mature resident cell types (transdifferentiation). Cell fate potential is programmed in tissue-specific configurations of chromatin, which restrict the complement of available genes and regulatory elements, hence allowing specific cell types to arise. Using as a model the transcriptional and chromatin basis of cell differentiation and dedifferentiation in intestinal crypts, we discuss here how self-renewing and other tissues execute homeostatic and injury-responsive stem cell activity.
成体组织干细胞的主要特性是自我更新以及生成多种驻留细胞类型的能力。终末分化的肠细胞、皮肤细胞和血细胞每日都会损耗，这就需要“专职”干细胞来产生替代细胞。这一过程通过干细胞及其直接子代的持续扩增来实现，随后不同转录程序协同激活，以生成具有多种功能的稳定细胞。其他组织的细胞更替缓慢，甚至几乎不发生更替，并且在兼性干细胞活性策略或成熟驻留细胞类型之间的相互转化（转分化）方面差异很大。细胞命运潜能由染色质的组织特异性构型编程，这限制了可用基因和调控元件的互补性，从而使得特定细胞类型得以产生。我们以肠隐窝细胞分化和去分化的转录及染色质基础为模型，在此讨论自我更新组织和其他组织如何执行稳态和损伤反应性干细胞活性。
