Evidence map›Paper›PMID 29192290›Full record

ArticleScientific reports2017

Direct conversion of human fibroblasts into hepatocyte-like cells by ATF5, PROX1, FOXA2, FOXA3, and HNF4A transduction.

Daiki Nakamori, Hiroki Akamine, Kazuo Takayama, Fuminori Sakurai, Hiroyuki Mizuguchi

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 5% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.

  1. Pooled it
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  11. TF-COMB - Discovering grammar of transcription factor binding sites.Computational and structural biotechnology journal · 2022
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  13. Cell-PermeableInternational journal of molecular sciences · 2021
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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

5 authors at 3 institutions in 1 country.

Daiki NakamoriLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan.
Hiroki AkamineLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan.
Kazuo TakayamaLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan.
Fuminori SakuraiLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan.
Hiroyuki MizuguchiLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan. mizuguch@phs.osaka-u.ac.jp.
Osaka University of Pharmaceutical Sciences · JPJapan Science and Technology Agency · JPNational Institute of Biomedical Innovation, Health and Nutrition · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recently, it has been reported that human hepatocyte-like cells can be generated from fibroblasts by direct reprogramming technology. However, the conversion efficiency of human induced hepatocyte-like cells (hiHeps) is not high enough. In addition, comparative analysis with the existing models of hepatocytes, such as human iPS cell-derived hepatocyte-like cells and primary human hepatocytes, has not been sufficiently carried out. In this study, we screened hepatic transcription factors for efficient direct hepatic reprogramming and compared hepatic functions between hiHeps and other existing hepatocyte models. We found that human fibroblasts were efficiently converted into hiHeps by using a combination of ATF5, PROX1, FOXA2, FOXA3, and HNF4A (albumin+/alpha-1 antitrypsin+ cells = 27%, asialoglycoprotein receptor 1+ cells = 22%). The CYP expression levels and CYP activities in hiHeps were higher than those in human iPS cell-derived hepatocyte-like cells, but lower than those in short-term (4 hr) cultured primary human hepatocytes and primary human hepatocytes collected immediately after thawing. These results suggested that functional hiHeps could be efficiently generated by ATF5, PROX1, FOXA2, FOXA3, and HNF4A transduction. We believe that hiHeps generated by our method will be useful for the drug-discovery activities such as hepatotoxicity screening and drug metabolism tests.

Indexed as

Activating Transcription FactorsBiomarkersCell LineCell TransdifferentiationCellular ReprogrammingFibroblastsGene Expression ProfilingGene Expression Regulation, DevelopmentalHepatocyte Nuclear Factor 3-betaHepatocyte Nuclear Factor 3-gammaHepatocyte Nuclear Factor 4HepatocytesHumansTranscription FactorsTranscriptomeTransduction, GeneticActivating Transcription FactorsATF5 protein, humanBiomarkersFOXA2 protein, humanFOXA3 protein, humanHepatocyte Nuclear Factor 3-betaHepatocyte Nuclear Factor 3-gammaHepatocyte Nuclear Factor 4HNF4A protein, humanTranscription Factors

Identifiers

PMID29192290
PMCPMC5709502
OpenAlexW2770650361

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Registered trials

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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.