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Updated: Apr 17, 2026

RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
Published on: November 26, 2018
Molecular mechanisms of induced pluripotency
Katarzyna Kulcenty1, Joanna Wróblewska1, Sylwia Mazurek2
1Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland ; Gene Therapy Laboratory, Department of Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
Abstract:
Growing knowledge concerning transcriptional control of cellular pluripotency has led to the discovery that the fate of differentiated cells can be reversed, which has resulted in the generation, by means of genetic manipulation, of induced pluripotent stem cells. Overexpression of just four pluripotency-related transcription factors, namely Oct3/4, Sox2, Klf4, and c-Myc (Yamanaka factors, OKSM), in fibroblasts appears sufficient to produce this new cell type. Currently, we know that these factors induce several changes in genetic program of differentiated cells that can be divided in two general phases: the initial one is stochastic, and the subsequent one is highly hierarchical and organised. This review briefly discusses the molecular events leading to induction of pluripotency in response to forced presence of OKSM factors in somatic cells. We also discuss other reprogramming strategies used thus far as well as the advantages and disadvantages of laboratory approaches towards pluripotency induction in different cell types.
Insights
Induced pluripotent stem cells (iPSCs) are generated by reprogramming differentiated cells using Yamanaka factors (OKSM). This review covers the molecular mechanisms, phases of reprogramming, and various strategies for inducing pluripotency.
Area of Science:
- Stem cell biology
- Molecular biology
- Genetics
Background:
- Cellular pluripotency and differentiation are key areas in developmental biology.
- Induced pluripotent stem cells (iPSCs) offer a route to reverse cell fate.
- The Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are crucial for reprogramming.
Purpose of the Study:
- To review the molecular events driving pluripotency induction by Yamanaka factors.
- To discuss different reprogramming strategies and their associated pros and cons.
- To explore laboratory approaches for inducing pluripotency in various cell types.
Main Methods:
- Genetic manipulation to overexpress specific transcription factors.
- Analysis of molecular events during the reprogramming process.
- Comparative review of different pluripotency induction strategies.
Main Results:
- Forced expression of Oct3/4, Sox2, Klf4, and c-Myc (OKSM) can reprogram somatic cells into iPSCs.
- Reprogramming involves distinct stochastic and hierarchical phases.
- Various reprogramming strategies exist, each with specific advantages and disadvantages.
Conclusions:
- Understanding the molecular mechanisms of pluripotency induction is critical for regenerative medicine.
- The OKSM factors initiate a complex cascade of genetic changes.
- Further research into optimizing reprogramming techniques is essential for diverse cell types.
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