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Reprogramming

When cellular reprogramming meets AI: towards de novo cell design

Nature Reviews Genetics volume 26, page 585 (2025)Cite this article

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Decoding and reprogramming cells — the fundamental units of life — remains one of the most profound challenges in modern biology. Historically, the identity of a differentiated cell was viewed as fixed, much like a marble rolling down Waddington’s epigenetic landscape, unable to return once it committed to a developmental path.

This dogma was challenged in 2006, when Shinya Yamanaka discovered that the forced expression of just four transcription factors, OCT3/4, SOX2, KLF4 and MYC (collectively known as OSKM), could reprogramme adult somatic cells back into an embryonic-like pluripotent state. This landmark discovery, which was awarded the 2012 Nobel Prize in Physiology or Medicine (shared with John B. Gurdon), demonstrated that cell fate is far more plastic than previously believed. Reading this paper as an undergraduate was my first academic ‘aha’ moment. Inspired by its elegance and implications, I decided to pursue my PhD to discover new cocktails for reprogramming cell states.

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  1. Cutaneous Biology Research Center, Harvard Medical School, Boston, MA, USA

    Jian Shu

  2. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Jian Shu

  3. Harvard-MIT Health Sciences and Technology, MIT, Cambridge, MA, USA

    Jian Shu

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  1. Jian Shu
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Correspondence to Jian Shu.

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Shu, J. When cellular reprogramming meets AI: towards de novo cell design. Nat Rev Genet 26, 585 (2025). https://doi.org/10.1038/s41576-025-00878-3

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