Evidence map›Paper›PMID 34525385›Full record

ArticleStem cell reports2021

High-throughput screening on cochlear organoids identifies VEGFR-MEK-TGFB1 signaling promoting hair cell reprogramming.

Qing Liu, Linqing Zhang, Min-Sheng Zhu, Guoqiang Wan

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

21 citing papers in PubMed, 24 citations in OpenAlex.

  1. Inner Ear Organoids: Recent Progress and Challenges.Stem cell reviews and reports · 2026
    Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
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  9. The Reconstruction of Peripheral Auditory Circuit: Recent Advances and Future Challenges.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  10. Review
  11. Review
  12. Metabolic Profiling of Cochlear Organoids Identifies α-Ketoglutarate and NADAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  13. Article
  14. Review
  15. Review
  16. Review
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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

4 authors at 1 institution in 1 country.

Qing LiuMOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing 210032, China.
Linqing ZhangMOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing 210032, China.
Min-Sheng ZhuMOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing 210032, China.
Guoqiang WanMOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing 210032, China; Research Institute of Otolaryngology, No. 321 Zhongshan Road, 210008 Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210032, China; Institute for Brain Sciences, Nanjing University, Nanjing 210032, China. Electronic address: guoqiangwan@nju.edu.cn.
Model Animal Research Center · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hair cell degeneration is a major cause of sensorineural hearing loss. Hair cells in mammalian cochlea do not spontaneously regenerate, posing a great challenge for restoration of hearing. Here, we establish a robust, high-throughput cochlear organoid platform that facilitates 3D expansion of cochlear progenitor cells and differentiation of hair cells in a temporally regulated manner. High-throughput screening of the FDA-approved drug library identified regorafenib, a VEGFR inhibitor, as a potent small molecule for hair cell differentiation. Regorafenib also promotes reprogramming and maturation of hair cells in both normal and neomycin-damaged cochlear explants. Mechanistically, inhibition of VEGFR suppresses TGFB1 expression via the MEK pathway and TGFB1 downregulation directly mediates the effect of regorafenib on hair cell reprogramming. Our study not only demonstrates the power of a cochlear organoid platform in high-throughput analyses of hair cell physiology but also highlights VEGFR-MEK-TGFB1 signaling crosstalk as a potential target for hair cell regeneration and hearing restoration.

Indexed as

Cellular ReprogrammingHigh-Throughput Screening AssaysAnimalsCell Culture Techniques, Three DimensionalCell DifferentiationCells, CulturedCochleaDrug DiscoveryDrug Evaluation, PreclinicalGene Expression RegulationHair Cells, AuditoryMiceMice, TransgenicMitogen-Activated Protein Kinase KinasesOrganoidsPhenylurea CompoundsLgr5 protein, mouseMitogen-Activated Protein Kinase KinasesPhenylurea CompoundsPyridinesReceptors, G-Protein-CoupledReceptors, Vascular Endothelial Growth FactorregorafenibTransforming Growth Factor beta1drug screeninghair cellsinner earorganoidsRegorafenibreprogramming

Identifiers

PMID34525385
PMCPMC8452601
OpenAlexW3201369843

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.