Evidence map›Paper›PMID 26449528›Full record

ArticleScientific reports2015

Directed Differentiation of Embryonic Stem Cells Into Cardiomyocytes by Bacterial Injection of Defined Transcription Factors.

Fang Bai, Chae Ho Lim, Jingyue Jia, Katherine Santostefano, Chelsey Simmons, Hideko Kasahara, Weihui Wu, Naohiro Terada, Shouguang Jin

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

25 citing papers in PubMed, 41 citations in OpenAlex.

  1. Review
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  5. Gene Editing and Human iPSCs in Cardiovascular and Metabolic Diseases.Advances in experimental medicine and biology · 2023
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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

9 authors at 2 institutions in 2 countries.

Fang BaiState Key Laboratory of Medicinal Chemical Biology and Colleges of Pharmacy and Life Sciences, Nankai University, Tianjin, China.
Chae Ho LimDepartment of Pathology College of Medicine, University of Florida, Gainesville, FL 32610.
Jingyue JiaState Key Laboratory of Medicinal Chemical Biology and Colleges of Pharmacy and Life Sciences, Nankai University, Tianjin, China.
Katherine SantostefanoDepartment of Pathology College of Medicine, University of Florida, Gainesville, FL 32610.
Chelsey SimmonsDepartment of Mechanical &Aerospace Engineering College of Engineering, University of Florida, Gainesville, FL 32611.
Hideko KasaharaDepartment of Physiology and Functional Genomics, University of Florida, College of Medicine, Gainesville, Florida, United States of America.
Weihui WuState Key Laboratory of Medicinal Chemical Biology and Colleges of Pharmacy and Life Sciences, Nankai University, Tianjin, China.
Naohiro TeradaDepartment of Pathology College of Medicine, University of Florida, Gainesville, FL 32610.
Shouguang JinState Key Laboratory of Medicinal Chemical Biology and Colleges of Pharmacy and Life Sciences, Nankai University, Tianjin, China.
University of Florida · USNankai University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Forced expression of defined transcriptional factors has been well documented as an effective method for cellular reprogramming or directed differentiation. However, transgene expression is not amenable for therapeutic application due to potential insertional mutagenesis. Here, we have developed a bacterial type III secretion system (T3SS)-based protein delivery tool and shown its application in directing pluripotent stem cell differentiation by a controlled delivery of transcription factors relevant to early heart development. By fusing to an N-terminal secretion sequence for T3SS-dependent injection, three transcriptional factors, namely Gata4, Mef2c, and Tbx5 (abbreviated as GMT), were translocated into murine embryonic stem cells (ESCs), where the proteins are effectively targeted to the nucleus with an average intracellular half-life of 5.5 hours. Exogenous GMT protein injection activated the cardiac program, and multiple rounds of GMT protein delivery significantly improved the efficiency of ESC differentiation into cardiomyocytes. Combination of T3SS-mediated GMT delivery and Activin A treatment showed an additive effect, resulting in on average 60% of the ESCs differentiated into cardiomyocytes. ESC derived cardiomyocytes displayed spontaneous rhythmic contractile movement as well as normal hormonal responses. This work serves as a foundation for the bacterial delivery of multiple transcription factors to direct cell fate without jeopardizing genomic integrity.

Indexed as

AnimalsBlotting, WesternCell DifferentiationCell LineCell NucleusGATA4 Transcription FactorGene ExpressionHeLa CellsHumansMEF2 Transcription FactorsMiceMicroscopy, FluorescenceMouse Embryonic Stem CellsMyocytes, CardiacPseudomonas aeruginosaReverse Transcriptase Polymerase Chain ReactionGata4 protein, mouseGATA4 Transcription FactorMef2c protein, mouseMEF2 Transcription FactorsT-Box Domain ProteinsT-box transcription factor 5Transcription Factors

Identifiers

PMID26449528
PMCPMC4598736
OpenAlexW2266448794

What OpenQuestion holds

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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.