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Updated: Sep 27, 2025
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Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency
Published on: June 10, 2018
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Chemical Pretreatment Activated a Plastic State Amenable to Direct Lineage Reprogramming
Zhenghao Yang1, Xiaochan Xu2, Chan Gu3
1State Key Laboratory of Natural and Biomimetic Drugs, MOE Key Laboratory of Cell Proliferation and Differentiation, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.
Frontiers in Cell and Developmental Biology
|April 11, 2022
Summary
Scientists discovered a new plastic chemically activated multi-lineage priming (CaMP) state that improves cell reprogramming efficiency. This state bypasses pluripotency, enabling direct conversion to neuron-like or muscle cells.
Area of Science:
- Cellular reprogramming
- Developmental biology
- Chemical biology
Background:
- Somatic cells can be chemically reprogrammed into pluripotent stem cells (CiPSCs) via an extraembryonic endoderm-like (XEN) state.
- The initial stages of chemical reprogramming involve a transient plastic state in fibroblasts.
Purpose of the Study:
- To investigate the characteristics of the initial plastic state during chemical reprogramming.
- To determine if this plastic state can enhance direct cell fate conversion.
- To explore if pluripotency is essential for generating functional cell types via chemical induction.
Main Methods:
- Chemical induction of mouse fibroblasts.
- Analysis of transcription factor expression and chromatin accessibility.
- Assessment of reprogramming efficiency towards neuron-like and skeletal muscle cells.
Main Results:
- Chemical reprogramming initially induces a plastic state with broad transcription factor activation and accessible chromatin.
- This plastic state significantly enhances direct reprogramming efficiency to functional neuron-like and skeletal muscle cells.
- Direct generation of neuron-like or muscle cells is achievable without an intermediate XEN-like or pluripotent state.
Conclusions:
- A plastic chemically activated multi-lineage priming (CaMP) state exists at the onset of chemical reprogramming.
- The CaMP state primes cells for fate conversion, improving reprogramming efficiency.
- This finding offers a general strategy for direct chemical reprogramming into desired cell types, bypassing pluripotency.
Keywords:
cell fate transitioncell plasticitychemical reprogrammingchromatin accessibilitydirect reprogrammingMore Related Videos
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