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Updated: Jun 14, 2025
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RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
Published on: November 26, 2018
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Programmable editing of primary MicroRNA switches stem cell differentiation and improves tissue regeneration
Vu Anh Truong1, Yu-Han Chang2,3, Thuc Quyen Dang1
1Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Nature Communications
|September 27, 2024
Summary
Researchers developed REPRESS, a novel RNA editing tool, to precisely modify primary microRNAs (pri-miRNAs). This technology enables targeted miRNA suppression for applications in stem cell reprogramming and tissue regeneration.
Area of Science:
- Molecular Biology
- RNA Therapeutics
- Biotechnology
Background:
- MicroRNAs (miRNAs) regulate diverse biological processes.
- Current RNA editing tools primarily target messenger RNA (mRNA), not miRNA precursors.
- Engineering primary miRNA (pri-miRNA) offers a new avenue for miRNA regulation.
Purpose of the Study:
- To develop a novel RNA editing system for precise manipulation of pri-miRNAs.
- To characterize the efficiency and specificity of the developed RNA editor.
- To explore the therapeutic potential of pri-miRNA editing in stem cell reprogramming and tissue regeneration.
Main Methods:
- Design and optimization of a customizable RNA editor, REPRESS (RNA Editing of Pri-miRNA for Efficient Suppression of miRNA).
- Editing of various pri-miRNAs in different cell types, including adipose-derived stem cells (ASCs).
- Development of an enhanced version, iREPRESS, for prolonged and enhanced pri-miR-21 editing.
Main Results:
- REPRESS enables editing of pri-miRNAs not editable by existing mRNA editing systems.
- Mature miRNA levels were attenuated without affecting host gene expression.
- iREPRESS demonstrated sustained editing for over 10 days with minimal transcriptome and miRNAome perturbation.
- iREPRESS successfully reprogrammed ASC differentiation, promoted cartilage formation, and enhanced bone regeneration in vivo.
Conclusions:
- REPRESS and iREPRESS are effective tools for engineering pri-miRNA.
- Pri-miRNA editing offers a promising strategy for stem cell reprogramming and tissue regeneration.
- This technology has significant potential for therapeutic applications in regenerative medicine.
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