Department of Systems Biology, Harvard Medical School, Boston MA, USA; Systems Biology PhD Program, Harvard University, Cambridge MA, USA.
Department of Systems Biology, Harvard Medical School, Boston MA, USA.
Curr Opin Biotechnol. 2018 Jun;51:109-115. doi: 10.1016/j.copbio.2017.12.007. Epub 2017 Dec 27.
Non-genetic heterogeneity fluctuates over diverse timescales, ranging from hours to months. In specific cases, such variability can profoundly impact the response of cell populations to therapy, in both antibiotic treatments in bacteria and chemotherapy in cancer. It is thus critical to understand the way phenotypes fluctuate in cell populations and the molecular sources of phenotypic diversity. Technical and analytical breakthroughs in the study of single cells have leveraged cellular heterogeneity to gain phenomenological and mechanistic insights of the phenotypic transitions that occur within isogenic cell populations over time. Such an understanding moves forward our ability to design therapeutic strategies with the explicit goal of preventing and controlling the selective expansion and stabilization of drug-tolerant phenotypic states.
非遗传异质性在不同的时间尺度上波动，范围从数小时到数月不等。在某些特定情况下，这种可变性会极大地影响细胞群体对治疗的反应，无论是在细菌的抗生素治疗还是癌症的化疗中。因此，了解细胞群体中表型的波动方式以及表型多样性的分子来源至关重要。单细胞研究中的技术和分析突破利用细胞异质性，深入了解在时间推移过程中同基因细胞群体中发生的表型转变的现象学和机制性见解。这种理解提高了我们设计治疗策略的能力，明确目标是防止和控制药物耐受表型状态的选择性扩张和稳定。
