Evidence map›Paper›PMID 28934500›Full record

ArticleNucleic acids research2017

A synthetic DNA-binding inhibitor of SOX2 guides human induced pluripotent stem cells to differentiate into mesoderm.

Junichi Taniguchi, Ganesh N Pandian, Takuya Hidaka, Kaori Hashiya, Toshikazu Bando, Kyeong Kyu Kim, Hiroshi Sugiyama

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.1field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 53 citations in OpenAlex.

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  12. Functional characterization of SOX2 as an anticancer target.Signal transduction and targeted therapy · 2020
    Review
  13. Repression of the transcriptional activity of ERRα with sequence-specific DNA-binding polyamides.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Junichi TaniguchiDepartment of Chemistry, Graduate School of Science Kyoto University, Sakyo-Ku, Kyoto 606-8502, Japan.
Ganesh N PandianInstitute for Integrated Cell-Materials Science (WPI-iCeMS) Kyoto University, Sakyo-Ku, Kyoto 606-8502, Japan.
Takuya HidakaDepartment of Chemistry, Graduate School of Science Kyoto University, Sakyo-Ku, Kyoto 606-8502, Japan.
Kaori HashiyaDepartment of Chemistry, Graduate School of Science Kyoto University, Sakyo-Ku, Kyoto 606-8502, Japan.
Toshikazu BandoDepartment of Chemistry, Graduate School of Science Kyoto University, Sakyo-Ku, Kyoto 606-8502, Japan.
Kyeong Kyu KimDepartment of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
Hiroshi SugiyamaDepartment of Chemistry, Graduate School of Science Kyoto University, Sakyo-Ku, Kyoto 606-8502, Japan.
Kyoto University · JPSungkyunkwan University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals would have value-added clinical potential in the regeneration of complex cell types including cardiomyocytes. Despite the availability of several chemical inhibitors targeting proteins involved in signaling pathways, no bioactive synthetic DNA-binding inhibitors, targeting key cell fate-controlling genes such as SOX2, are yet available. Here, we demonstrate a novel DNA-based chemical approach to guide the differentiation of hiPSCs using pyrrole-imidazole polyamides (PIPs), which are sequence-selective DNA-binding synthetic molecules. Harnessing knowledge about key transcriptional changes during the induction of cardiomyocyte, we developed a DNA-binding inhibitor termed PIP-S2, targeting the 5'-CTTTGTT-3' and demonstrated that inhibition of SOX2-DNA interaction by PIP-S2 triggers the mesoderm induction in hiPSCs. Genome-wide gene expression analyses revealed that PIP-S2 induced mesoderm by targeted alterations in SOX2-associated gene regulatory networks. Also, employment of PIP-S2 along with a Wnt/β-catenin inhibitor successfully generated spontaneously contracting cardiomyocytes, validating our concept that DNA-binding inhibitors could drive the directed differentiation of hiPSCs. Because PIPs can be fine-tuned to target specific DNA sequences, our DNA-based approach could be expanded to target and regulate key transcription factors specifically associated with desired cell types.

Indexed as

Base SequenceBinding SitesCell DifferentiationCell LineConsensus SequenceGene ExpressionHumansInduced Pluripotent Stem CellsMesodermMyocytes, CardiacNylonsPyrrolesSOXB1 Transcription FactorsWnt Signaling PathwayNylonsPIP-S2 compoundPyrrolesSOX2 protein, humanSOXB1 Transcription Factors

Identifiers

PMID28934500
PMCPMC5766170
OpenAlexW2740134080

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.