Programmable editing of primary MicroRNA switches stem cell differentiation and improves tissue regeneration

V.A. Truong; Y.-H. Chang; T.Q. Dang; Y. Tu; J. Tu; C.-W. Chang; G.-S. Liu; Y.-C. Hu

doi:10.1038/s41467-024-52707-6

期刊文章

Programmable editing of primary MicroRNA switches stem cell differentiation and improves tissue regeneration

V.A. Truong, Y.-H. Chang, T.Q. Dang, Y. Tu, J. Tu, C.-W. Chang, Y.-H. Chang, G.-S. Liu 和 Y.-C. Hu

Nature Communications, 卷.15(1)

2024

DOI: https://doi.org/10.1038/s41467-024-52707-6

Web of Science ID: WOS:001377340000036

摘要

Adipose Tissue

Animals

Bone Regeneration

Cell Differentiation

Humans

Male

MicroRNAs

Rats

Rats, Sprague-Dawley

Regeneration

RNA Editing

Stem Cells

messenger RNA

microRNA

transcriptome

microRNA

mirn21 microRNA, rat

bioengineering

bone

cell component

differentiation

RNA

adipose derived stem cell

animal model

Article

bone regeneration

calvaria

cartilage

cell differentiation

cell metabolism

controlled study

gene expression

HEK293-FT cell line

human

human cell

in vitro study

micro-computed tomography

nonhuman

nuclear reprogramming

rat

reverse transcription

RNA editing

RNA sequencing

stem cell

tissue regeneration

adipose tissue

animal

cytology

genetics

male

metabolism

physiology

regeneration

Sprague Dawley rat

Programmable RNA editing is harnessed for modifying mRNA. Besides mRNA, miRNA also regulates numerous biological activities, but current RNA editors have yet to be exploited for miRNA manipulation. To engineer primary miRNA (pri-miRNA), the miRNA precursor, we present a customizable editor REPRESS (RNA Editing of Pri-miRNA for Efficient Suppression of miRNA) and characterize critical parameters. The optimized REPRESS is distinct from other mRNA editing tools in design rationale, hence enabling editing of pri-miRNAs that are not editable by other RNA editing systems. We edit various pri-miRNAs in different cells including adipose-derived stem cells (ASCs), hence attenuating mature miRNA levels without disturbing host gene expression. We further develop an improved REPRESS (iREPRESS) that enhances and prolongs pri-miR-21 editing for at least 10 days, with minimal perturbation of transcriptome and miRNAome. iREPRESS reprograms ASCs differentiation, promotes in vitro cartilage formation and augments calvarial bone regeneration in rats, thus implicating its potentials for engineering miRNA and applications such as stem cell reprogramming and tissue regeneration. © The Author(s) 2024.

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詳細資料

題名: Programmable editing of primary MicroRNA switches stem cell differentiation and improves tissue regeneration
創作者：: V.A. Truong - National Tsing Hua University
Y.-H. Chang - National Tsing Hua University
T.Q. Dang - National Tsing Hua University
Y. Tu - National Taiwan University
J. Tu - National Taiwan University
C.-W. Chang - National Tsing Hua University
Y.-H. Chang - National Tsing Hua University
G.-S. Liu - University of Tasmania
Y.-C. Hu - National Tsing Hua University
出版者: Nature Research; BERLIN
總頁數: 14
補助款備註: National Health Research Institutes (NHRI): 112-2223-E-007-002, 112-2314-B-007-004-MY3, 111-2223-E-007-003, 111-2634-F-007-007, 111-2622-E-007-003, 109-2314-B-007-002-MY3 National Science and Technology Council (NSTC): CMRPG3M0782, CMRPG3M0781 Chang Gung Memorial Hospital: NHRI-EX112-11014BI, NHRI-EX113-11329EI National Health Research Institutes
The authors thank the Laboratory Animal Center, Chang Gung Memorial Hospital, Linkou, Taiwan for the molecular imaging and technical support. The authors also acknowledge the financial support from the National Science and Technology Council (NSTC 112-2223-E-007-002 (Y.C.H.), 112-2314-B-007-004-MY3 (Y.C.H.), 111-2223-E-007-003 (Y.C.H.), 111-2634-F-007-007 (Y.C.H.), 111-2622-E-007-003 (Y.C.H.), 109-2314-B-007-002-MY3 (Y.C.H.)), Chang Gung Memorial Hospital (CMRPG3M0782 (Y.C.H.), CMRPG3M0781 (Y.C.H.)) and National Health Research Institutes (NHRI-EX112-11014BI (Y.C.H.), NHRI-EX113-11329EI (Y.C.H.)), Taiwan.
學術資源類型: 期刊文章
出版日期: 2024
出版資訊: Nature Communications, 卷.15(1)
語言: 英語

Programmable editing of primary MicroRNA switches stem cell differentiation and improves tissue regeneration

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