Evidence map›Paper›PMID 24586731›Full record

ArticlePloS one2014

In vivo generation of immature inner hair cells in neonatal mouse cochleae by ectopic Atoh1 expression.

Zhiyong Liu, Jie Fang, Jennifer Dearman, Lingli Zhang, Jian Zuo

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
5.5field-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

70 citing papers in PubMed, 98 citations in OpenAlex.

  1. Article
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  9. Reprogramming withPNAS nexus · 2024
    Article
  10. Review
  11. Article
  12. AAV-mediated Gene Cocktails Enhance Supporting Cell Reprogramming and Hair Cell Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  13. Hair Cell Regeneration: From Animals to Humans.Clinical and experimental otorhinolaryngology · 2024
    Review
  14. The transcription factorFrontiers in cellular neuroscience · 2024
    Article
  15. Fgf8Neuroscience bulletin · 2023
    Article
  16. Article
  17. Reprogramming by drug-like molecules leads to regeneration of cochlear hair cell-like cells in adult mice.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  18. Article
  19. Review
  20. Article

10 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Zhiyong LiuDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America ; Integrated Program In Biomedical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Jie FangDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Jennifer DearmanDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Lingli ZhangDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Jian ZuoDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
St. Jude Children's Research Hospital · USUniversity of Tennessee Health Science Center · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
GENETIC ANALYSIS OF MAMMALIAN HEARING SENSITIVITYR01DC006471 · NIDCD · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI ZUO, JIAN · 2004 to 2013
$3.5M
Generation of mice with inducible Cre expression in adult cochlear hair cellsR21DC008800 · NIDCD · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI ZUO, JIAN · 2007 to 2008
$410k
NCI NIH HHS CA21765NCI NIH HHS P30 CA021765NIDCD NIH HHS DC006471NIDCD NIH HHS DC008800NIDCD NIH HHS R01 DC006471NIDCD NIH HHS R21 DC008800
6 · The paper itself

Abstract

Regeneration of auditory hair cells (HCs) is a promising approach to restore hearing. Recent studies have demonstrated that induced pluripotent stem cells/embryonic stem cells or supporting cells (SCs) adjacent to HCs can be converted to adopt the HC fate. However, little is known about whether new HCs are characteristic of outer or inner HCs. Here, we showed in vivo conversion of 2 subtypes of SCs, inner border cells (IBs) and inner phalangeal cells (IPhs), to the inner HC (IHC) fate. This was achieved by ectopically activating Atoh1, a transcription factor necessary for HC fate, in IBs/IPhs at birth. Atoh1+ IBs/IPhs first turned on Pou4f3, another HC transcription factor, before expressing 8 HC markers. The conversion rate gradually increased from ∼ 2.4% at 1 week of age to ∼ 17.8% in adult. Interestingly, new HCs exhibited IHC characteristics such as straight line-shaped stereociliary bundles, expression of Fgf8 and otoferlin, and presence of larger outward currents than those of outer HCs. However, new HCs lacked the terminal differentiation IHC marker vGlut3, exhibited reduced density of presynaptic Cbtp2 puncta that had little postsynaptic GluR2 specialization, and displayed immature IHC outward currents. Our results demonstrate that the conversion rate of IBs/IPhs in vivo by Atoh1 ectopic expression into the IHC fate was higher and faster and the conversion was more complete than that of the 2 other SC subtypes underneath the outer HCs; however, these new IHCs are arrested before terminal differentiation. Thus, IBs/IPhs are good candidates to regenerate IHCs in vivo.

Indexed as

Gene Expression Regulation, DevelopmentalAmino Acid Transport Systems, AcidicAnimalsAnimals, NewbornBasic Helix-Loop-Helix ProteinsCell DifferentiationCochleaElectrophysiologyFibroblast Growth Factor 8Fluorescent Antibody TechniqueHair Cells, Auditory, InnerHomeodomain ProteinsIn Situ HybridizationIn Situ Hybridization, FluorescenceMembrane ProteinsMiceAmino Acid Transport Systems, AcidicAtoh1 protein, mouseBasic Helix-Loop-Helix ProteinsFgf8 protein, mouseFibroblast Growth Factor 8Homeodomain ProteinsMembrane Proteinsotoferlin protein, mousePou4f3 protein, mouseSlc17a8 protein, mouseTranscription Factor Brn-3C

Identifiers

PMID24586731
PMCPMC3930725
OpenAlexW2078891648

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.