Evidence map›Paper›PMID 23842490›Full record

ArticleNature2013

Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture.

Karl R Koehler, Andrew M Mikosz, Andrei I Molosh, Dharmeshkumar Patel, Eri Hashino

Open access · greenAbstract read
In one paragraph

Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 218 papers.

0numbers the graph read from it
0cells of the map it votes in
218citing papers in PubMed
17.8field-weighted citation impact, top 1% 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

218 citing papers in PubMed, 400 citations in OpenAlex.

  1. Article
  2. Inner Ear Organoids: Recent Progress and Challenges.Stem cell reviews and reports · 2026
    Review
  3. Functionalized Biomimetic Scaffolds for Human-Derived Auditory Neural Circuit Construction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. The Reconstruction of Peripheral Auditory Circuit: Recent Advances and Future Challenges.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  16. AAV-Sparcl1 promotes hair cell regeneration by increasing supporting cell plasticity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  17. Retinoic acid receptor assembly dynamics governs dual functions in cochlear organogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Review
  19. Review
  20. Review

158 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.

Karl R KoehlerMedical Neuroscience Graduate Program, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Andrew M Mikosz
Andrei I Molosh
Dharmeshkumar Patel
Eri Hashino
Indiana University School of MedicineIndiana University – Purdue University Indianapolis · US

Funding

NEUROBIOLOGY OF PANIC AND ANXIETY DISORDERSR01MH052619 · NIMH · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SHEKHAR, ANANTHA · 1996 to 2016
$5.0M
Ligand Directed Functional Selectivity of G-Protein Coupled Receptor SignallingR01GM086544 · NIGMS · INDIANA UNIVERSITY INDIANAPOLIS · PI OXFORD, GERRY S · 2009 to 2012
$1.3M
Somatic Stem Cells as Vectors to Deliver Biologically Active Molecules to the InnRC1DC010706 · NIDCD · INDIANA UNIVERSITY INDIANAPOLIS · PI HASHINO, ERI · 2009 to 2010
$843k
Indiana Clinical and Translational Science Institute-T32 Program TL1TL1RR025759 · NCRR · INDIANA UNIVERSITY INDIANAPOLIS · PI SHEKHAR, ANANTHA · 2008 to 2011
$710k
Induced Pluripotent Stem Cells for Modeling Congenital DeafnessR21DC012617 · NIDCD · INDIANA UNIVERSITY INDIANAPOLIS · PI HASHINO, ERI · 2013 to 2014
$429k
NCRR NIH HHS TL1 RR025759NCRR NIH HHS TL1RR025759NIDCD NIH HHS R21 DC012617NIDCD NIH HHS R21DC012617NIDCD NIH HHS RC1 DC010706NIDCD NIH HHS RC1DC010706NIGMS NIH HHS R01 GM086544NIGMS NIH HHS R01GM086544NIMH NIH HHS R01 MH052619NIMH NIH HHS R01MH52619
6 · The paper itself

Abstract

The inner ear contains sensory epithelia that detect head movements, gravity and sound. It is unclear how to develop these sensory epithelia from pluripotent stem cells, a process that will be critical for modelling inner ear disorders or developing cell-based therapies for profound hearing loss and balance disorders. So far, attempts to derive inner ear mechanosensitive hair cells and sensory neurons have resulted in inefficient or incomplete phenotypic conversion of stem cells into inner-ear-like cells. A key insight lacking from these previous studies is the importance of the non-neural and preplacodal ectoderm, two critical precursors during inner ear development. Here we report the stepwise differentiation of inner ear sensory epithelia from mouse embryonic stem cells (ESCs) in three-dimensional culture. We show that by recapitulating in vivo development with precise temporal control of signalling pathways, ESC aggregates transform sequentially into non-neural, preplacodal and otic-placode-like epithelia. Notably, in a self-organized process that mimics normal development, vesicles containing prosensory cells emerge from the presumptive otic placodes and give rise to hair cells bearing stereocilia bundles and a kinocilium. Moreover, these stem-cell-derived hair cells exhibit functional properties of native mechanosensitive hair cells and form specialized synapses with sensory neurons that have also arisen from ESCs in the culture. Finally, we demonstrate how these vesicles are structurally and biochemically comparable to developing vestibular end organs. Our data thus establish a new in vitro model of inner ear differentiation that can be used to gain deeper insight into inner ear development and disorder.

Indexed as

Cell DifferentiationAnimalsCell Culture TechniquesEar, InnerElectrical SynapsesGene Expression Regulation, DevelopmentalHair Cells, Auditory, InnerHumansMiceMyosinsMyosin VIIaNeurogenesisPluripotent Stem CellsRecombinant ProteinsMYO7A protein, humanMyo7a protein, mouseMyosinsMyosin VIIaRecombinant Proteins

Identifiers

PMID23842490
PMCPMC3739998
OpenAlexW1967800133

What OpenQuestion holds

Textmetadata
LicenceTDM
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.