4.7 Review

Single-Cell Genomics: Catalyst for Cell Fate Engineering

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fbioe.2021.748942

Keywords

reprogramming; single cell genomics; regenerative medicine; cell fate; transcription factor

Funding

  1. CPRIT [RP190451]
  2. NIH [DP2GM128203, UM1HG011996]
  3. Welch Foundation [I-1926-20170325]
  4. Burroughs Wellcome Fund [1019804]
  5. Green Center for Reproductive Biology

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As we approach a comprehensive catalog of mammalian cell types, the ability to engineer specific cell types on demand would revolutionize biomedical research and regenerative medicine. Direct reprogramming of cells through specific transcription factor cocktails offers a promising strategy for cell fate engineering. Recent advancements in single-cell technologies have overcome challenges in bulk reprogramming methods, accelerating progress in the field of cellular engineering.
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.

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