Single-Cell Genomics: Catalyst for Cell Fate Engineering.
Single-Cell Genomics: Catalyst for Cell Fate Engineering.
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DOI：
10.3389/fbioe.2021.748942
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发表时间：
2021
影响因子：
5.7
通讯作者：
Hon GC
中科院分区：
文献类型：
--
作者：
Li B;Hon GC
当我们接近一个完整的哺乳动物细胞类型目录时，根据需要设计特定细胞类型的能力将改变生物医学研究和再生医学。然而，目前发现新细胞类型的速度远远超过了我们设计它们的能力。细胞工程的一个有吸引力的策略是直接重编程，其中特异性转录因子（TF）鸡尾酒的诱导协调细胞状态转变。在这里，我们回顾TF介导的重编程的基础研究的背景下，细胞命运工程，其中包括：发现新的重编程鸡尾酒，评估工程细胞，并揭示分子机制的一般框架。传统的批量重编程方法为TF介导的重编程奠定了坚实的基础，但受到其小规模和难以解决细胞异质性的限制。最近，单细胞技术已经克服了这些挑战，迅速加快了细胞命运工程的进展。在接下来的十年里，我们预计这些工具将实现前所未有的细胞状态控制。
As we near a complete catalog of mammalian cell types, the capability to engineer specific cell types on demand would transform biomedical research and regenerative medicine. However, the current pace of discovering new cell types far outstrips our ability to engineer them. One attractive strategy for cellular engineering is direct reprogramming, where induction of specific transcription factor (TF) cocktails orchestrates cell state transitions. Here, we review the foundational studies of TF-mediated reprogramming in the context of a general framework for cell fate engineering, which consists of: discovering new reprogramming cocktails, assessing engineered cells, and revealing molecular mechanisms. Traditional bulk reprogramming methods established a strong foundation for TF-mediated reprogramming, but were limited by their small scale and difficulty resolving cellular heterogeneity. Recently, single-cell technologies have overcome these challenges to rapidly accelerate progress in cell fate engineering. In the next decade, we anticipate that these tools will enable unprecedented control of cell state.