Evidence map›Paper›PMID 26639555›Full record

ArticleNature communications2015

Cell cycle and p53 gate the direct conversion of human fibroblasts to dopaminergic neurons.

Houbo Jiang, Zhimin Xu, Ping Zhong, Yong Ren, Gaoyang Liang, Haley A Schilling, Zihua Hu, Yi Zhang, Xiaomin Wang, Shengdi Chen and 2 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

81 citing papers in PubMed, 130 citations in OpenAlex.

  1. Article
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  7. Review
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  9. Progress in direct reprogramming of dopaminergic cell replacement therapy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Review
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21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 2 countries.

Houbo JiangVeterans Affairs Western New York Healthcare System, Buffalo, New York 14215, USA.
Zhimin XuDepartment of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214, USA.
Ping ZhongVeterans Affairs Western New York Healthcare System, Buffalo, New York 14215, USA.
Yong RenDepartment of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214, USA.
Gaoyang LiangHoward Hughes Medical Institute, Departments of Genetics &Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Haley A SchillingDepartment of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214, USA.
Zihua HuCenter for Computational Research, New York State Center of Excellence in Bioinformatics &Life Sciences, State University of New York at Buffalo, Buffalo, New York 14260, USA.
Yi ZhangHoward Hughes Medical Institute, Departments of Genetics &Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Xiaomin WangDepartment of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China.
Shengdi ChenDepartment of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Zhen YanVeterans Affairs Western New York Healthcare System, Buffalo, New York 14215, USA.
Jian FengVeterans Affairs Western New York Healthcare System, Buffalo, New York 14215, USA.
University at Buffalo, State University of New York · USChinese Institute for Brain Research · CNHarvard University · USRuijin Hospital · CNShanghai Jiao Tong University · CNVA Western New York Healthcare System · US

Funding

Physiological and Pathophysiological Basis of StressR01MH108842 · NIMH · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI YAN, ZHEN · 2015 to 2019
$2.0M
Cellular Functions of ParkinR01NS061856 · NINDS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI FENG, JIAN · 2009 to 2013
$1.7M
Functions of D4 Dopamine Receptors in Prefrontal CortexR01DA037618 · NIDA · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI YAN, ZHEN · 2014 to 2018
$1.7M
A Novel Pathophysiological Mechanism of Alzheimer's DiseaseI01BX001633 · VA · VA WESTERN NEW YORK HEALTHCARE SYSTEM · PI YAN, ZHEN · 2013 to 2016
–
Kinetic Barriers of TransdifferentiationI01BX002452 · VA · VA WESTERN NEW YORK HEALTHCARE SYSTEM · PI FENG, JIAN · 2014 to 2021
–
BLRD VA I01 BX001633BLRD VA I01 BX002452NIDA NIH HHS R01 DA037618NIMH NIH HHS R01 MH108842NINDS NIH HHS NS061856NINDS NIH HHS R01 NS061856
6 · The paper itself

Abstract

The direct conversion of fibroblasts to induced dopaminergic (iDA) neurons and other cell types demonstrates the plasticity of cell fate. The low efficiency of these relatively fast conversions suggests that kinetic barriers exist to safeguard cell-type identity. Here we show that suppression of p53, in conjunction with cell cycle arrest at G1 and appropriate extracellular environment, markedly increase the efficiency in the transdifferentiation of human fibroblasts to iDA neurons by Ascl1, Nurr1, Lmx1a and miR124. The conversion is dependent on Tet1, as G1 arrest, p53 knockdown or expression of the reprogramming factors induces Tet1 synergistically. Tet1 knockdown abolishes the transdifferentiation while its overexpression enhances the conversion. The iDA neurons express markers for midbrain DA neurons and have active dopaminergic transmission. Our results suggest that overcoming these kinetic barriers may enable highly efficient epigenetic reprogramming in general and will generate patient-specific midbrain DA neurons for Parkinson's disease research and therapy.

Indexed as

Basic Helix-Loop-Helix ProteinsCell CycleCell Cycle CheckpointsCell LineCell TransdifferentiationCellular ReprogrammingDNA-Binding ProteinsDopaminergic NeuronsFibroblastsG1 Phase Cell Cycle CheckpointsGene Knockdown TechniquesHumansLIM-Homeodomain ProteinsMesencephalonMicroRNAsMixed Function OxygenasesASCL1 protein, humanBasic Helix-Loop-Helix ProteinsDNA-Binding ProteinsLIM-Homeodomain ProteinsLMX1A protein, humanMicroRNAsMIRN124 microRNA, humanMixed Function OxygenasesNR4A2 protein, humanNuclear Receptor Subfamily 4, Group A, Member 2Proto-Oncogene ProteinsTET1 protein, humanTP53 protein, humanTranscription FactorsTumor Suppressor Protein p53

Identifiers

PMID26639555
PMCPMC4672381
OpenAlexW2268912752

What OpenQuestion holds

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LicenceCC BY
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.