Evidence map›Paper›PMID 40575763›Full record

ArticleRegenerative biomaterials2025

Y-shaped DNA as a dynamic self-assembly nanomaterial for phenotype-specific regulation of stem cell differentiation on the gene level.

Wengang Liu, Ruili Liu, Lok Ting Chu, Xinlei Wang, Jianpeng Wu, Jiandong Ding, Ting Hsuan Chen

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Article in Regenerative biomaterials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Wengang LiuDepartment of Biomedical Engineering, City University of Hong Kong, Hong Kong Special Administrative Region 999077, China.
Ruili LiuState Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China.
Lok Ting ChuDepartment of Biochemistry and Molecular Biology, Guang Dong Medical University, Zhanjiang 524023, China.
Xinlei WangState Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China.
Jianpeng WuDepartment of Biomedical Engineering, City University of Hong Kong, Hong Kong Special Administrative Region 999077, China.
Jiandong DingState Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China.
Ting Hsuan ChenDepartment of Biomedical Engineering, City University of Hong Kong, Hong Kong Special Administrative Region 999077, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

While genetic engineering has offered new strategies for regulating stem cell differentiation, the efficacy varies in cells with different phenotypes or lineage commitments, leading to inconsistent differentiation outcomes and uncertainty in regenerative medicine. To address this issue, we employ a Y-shaped DNA (Y-DNA) as a nanomaterial to phenotype-specifically regulate differentiation of human mesenchymal stem cells (hMSCs). Y-DNA is composed of three DNA strands with complementary sequences and different roles. The Y-DNA designed in the present study can be uniquely activated by miR-106a-5p, a microRNA preferentially expressed in adipogenesis-biased hMSCs. Upon activation, the Y-DNA disassembles, releasing an antisense oligonucleotide that inhibits expression of cofilin, which serves as a key regulator to enhance adipogenic differentiation, and thus, prevents hMSCs from undergoing osteogenic differentiation. The key regulatory role of cofilin in hMSC differentiation is verified at the single-cell level on arginine-glycine-aspartate microislands under the nonfouling background of poly(ethylene glycol) hydrogels. Our strategy effectively redirects these cells towards osteogenic differentiation by inhibiting adipogenic differentiation, demonstrating dose dependence with high specificity, selectivity, and low toxicity. hMSCs cultured in a dual induction medium (a mixture of adipogenic medium and osteogenic medium) show enhanced osteogenic differentiation after transfection with the nanostructured Y-DNA. This approach addresses the challenge of cell heterogeneity in bone regeneration, offering a promising solution for precise control over stem cell fate. The ability of Y-DNA to specifically target cells with a propensity for adipogenic differentiation and to reprogram their lineage commitment has significant implications for the field of regenerative medicine, particularly in applications requiring enhanced purity of cell differentiation outcomes.

Indexed as

antisense oligonucleotidegene regulationmesenchymal stem cellmicropatternosteogenic differentiationpoly(ethylene glycol)Y-shaped DNA

Identifiers

PMID40575763
PMCPMC12202102

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.