Wang Nathan B, Beitz Adam M, Galloway Kate E
Department of Chemical Engineering, MIT, 25 Ames St., Cambridge, MA, 02139, USA.
Curr Opin Syst Biol. 2020 Dec;24:18-31. doi: 10.1016/j.coisb.2020.09.002. Epub 2020 Sep 21.
Cellular reprogramming drives cells from one stable identity to a new cell fate. By generating a diversity of previously inaccessible cell types from diverse genetic backgrounds, cellular reprogramming is rapidly transforming how we study disease. However, low efficiency and limited maturity have limited the adoption of -derived cellular models. To overcome these limitations and improve mechanistic understanding of cellular reprogramming, a host of synthetic biology tools have been deployed. Recent synthetic biology approaches have advanced reprogramming by tackling three significant challenges to reprogramming: delivery of reprogramming factors, epigenetic roadblocks, and latent donor identity. In addition, emerging insight from the molecular systems biology of reprogramming reveal how systems-level drivers of reprogramming can be harnessed to further advance reprogramming technologies. Furthermore, recently developed synthetic biology tools offer new modes for engineering cell fate.
细胞重编程驱动细胞从一种稳定状态转变为新的细胞命运。通过从不同的遗传背景中生成多种以前难以获得的细胞类型,细胞重编程正在迅速改变我们研究疾病的方式。然而,低效率和有限的成熟度限制了诱导多能干细胞衍生的细胞模型的应用。为了克服这些限制并增进对细胞重编程机制的理解,人们已经部署了一系列合成生物学工具。最近的合成生物学方法通过应对重编程的三个重大挑战推动了重编程的发展:重编程因子的递送、表观遗传障碍和潜在的供体身份。此外,重编程分子系统生物学的新见解揭示了如何利用重编程的系统水平驱动因素来进一步推进重编程技术。此外,最近开发的合成生物学工具为设计细胞命运提供了新的模式。