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Tracking induced pluripotent stem cells differentiation with a fluorescent genetically encoded epigenetic probe
2024-10-09 40

Affiliations

  • Skolkovo Institute of Science and Technology, Bolshoi Blvd. 30, Bld. 1, 121205, Moscow, Russia.
  • Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
  • Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russia.
  • Pirogov Russian National Research Medical University, Ostrovityanova 1, 117997, Moscow, Russia.
  • Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow, 117997, Russia.
  • The Scintillon Research Institute, 6404 Nancy Ridge Dr., San Diego, CA, 92121, USA.
  • Corresponding authors: gurskayanadya@gmail.com

PMID:  39222083 PMCID: PMC11368889 DOI: 10.1007/s00018-024-05359-0

Abstract

Background: Epigenetic modifications, such as methylation and acetylation, regulate gene expression and change dynamically during cell differentiation and dedifferentiation. This study introduces a genetically encoded fluorescent probe, MPP8-Green, to visualize the epigenetic landscape in live cells.

Methods: The MPP8-Green probe targets H3K9me3 histone modifications and tracks changes during the differentiation of induced pluripotent stem cells (iPSCs) into neurons. The study introduces LiveMIEL (Live-cell Microscopic Imaging of Epigenetic Landscapes), combining probes and machine learning for real-time classification.

Results: H3K9me3 reorganization occurs in two distinct waves during the differentiation process, suggesting a complex mechanism in chromatin dynamics.

Conclusion: The new method facilitates single-cell analysis of epigenetic signatures and can be applied to various biological models.

Keywords

Epigenetics; Fluorescent proteins; Genetically encoded sensor; H3K9me3; Histone modification; Machine learning.

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