Evidence map›Paper›PMID 32678240›Full record

ArticleScientific reports2020

Dual SMAD inhibition and Wnt inhibition enable efficient and reproducible differentiations of induced pluripotent stem cells into retinal ganglion cells.

Venkata R M Chavali, Naqi Haider, Sonika Rathi, Vrathasha Vrathasha, Teja Alapati, Jie He, Kamaljot Gill, Roman Nikonov, Thu T Duong, Devin S McDougald and 3 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.6field-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

34 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Variant-to-gene mapping identifiesbioRxiv : the preprint server for biology · 2026
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  7. Rekindling Vision: Innovative Strategies for Treating Retinal Degeneration.International journal of molecular sciences · 2025
    Review
  8. Frontiers in cell and developmental biology · 2025
    Review
  9. Review
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  11. Article
  12. Review
  13. OPA1 Dominant Optic Atrophy: Pathogenesis and Therapeutic Targets.Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society · 2023
    Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
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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

13 authors at 3 institutions in 1 country.

Venkata R M ChavaliScheie Eye Institute, University of Pennsylvania Perelman School of Medicine, 133A Anatomy Chemistry Building, 3620 Hamilton Walk, Philadelphia, PA, 19104, USA. vchavali@pennmedicine.upenn.edu.
Naqi HaiderScheie Eye Institute, University of Pennsylvania Perelman School of Medicine, 133A Anatomy Chemistry Building, 3620 Hamilton Walk, Philadelphia, PA, 19104, USA.
Sonika RathiScheie Eye Institute, University of Pennsylvania Perelman School of Medicine, 133A Anatomy Chemistry Building, 3620 Hamilton Walk, Philadelphia, PA, 19104, USA.
Vrathasha VrathashaScheie Eye Institute, University of Pennsylvania Perelman School of Medicine, 133A Anatomy Chemistry Building, 3620 Hamilton Walk, Philadelphia, PA, 19104, USA.
Teja AlapatiScheie Eye Institute, University of Pennsylvania Perelman School of Medicine, 133A Anatomy Chemistry Building, 3620 Hamilton Walk, Philadelphia, PA, 19104, USA.
Jie HeScheie Eye Institute, University of Pennsylvania Perelman School of Medicine, 133A Anatomy Chemistry Building, 3620 Hamilton Walk, Philadelphia, PA, 19104, USA.
Kamaljot GillF.M. Kirby Center for Molecular Ophthalmology and Center for Advanced Retinal and Ocular Therapeutics (CAROT), 309B Stellar Chance Laboratories, Philadelphia, PA, 19104, USA.
Roman NikonovF.M. Kirby Center for Molecular Ophthalmology and Center for Advanced Retinal and Ocular Therapeutics (CAROT), 309B Stellar Chance Laboratories, Philadelphia, PA, 19104, USA.
Thu T DuongF.M. Kirby Center for Molecular Ophthalmology and Center for Advanced Retinal and Ocular Therapeutics (CAROT), 309B Stellar Chance Laboratories, Philadelphia, PA, 19104, USA.
Devin S McDougaldF.M. Kirby Center for Molecular Ophthalmology and Center for Advanced Retinal and Ocular Therapeutics (CAROT), 309B Stellar Chance Laboratories, Philadelphia, PA, 19104, USA.
Sergei NikonovF.M. Kirby Center for Molecular Ophthalmology and Center for Advanced Retinal and Ocular Therapeutics (CAROT), 309B Stellar Chance Laboratories, Philadelphia, PA, 19104, USA.
Joan O'BrienScheie Eye Institute, University of Pennsylvania Perelman School of Medicine, 133A Anatomy Chemistry Building, 3620 Hamilton Walk, Philadelphia, PA, 19104, USA.
Jason A MillsF.M. Kirby Center for Molecular Ophthalmology and Center for Advanced Retinal and Ocular Therapeutics (CAROT), 309B Stellar Chance Laboratories, Philadelphia, PA, 19104, USA. millsja@pennmedicine.upenn.edu.
Star Center · USUniversity of Pennsylvania · USPenn Presbyterian Medical Center · US

Funding

Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5M
Primary Open Angle African-American Glaucoma Genetics Study RenewalR01EY023557 · NEI · UNIVERSITY OF PENNSYLVANIA · PI O'BRIEN, JOAN M · 2014 to 2025
$18.1M
Deciphering the role of lipid metabolism pathways in the RPE and their implications for AMDR21EY028273 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CHAVALI, VENKATA RAMANA MURTHY · 2018 to 2019
$443k
Molecular Profiling of CRB1 Mutant Retinal Cells Derived from IPSC'sR21EY027936 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MILLS, JASON A · 2018 to 2019
$427k
NEI NIH HHS 1RO1EY023557-01NEI NIH HHS HHSN263201200001CNEI NIH HHS P30 EY001583NEI NIH HHS P30EY01583-26NEI NIH HHS R01 EY023557NEI NIH HHS R21 EY027936NEI NIH HHS R21EY027936-01A1NEI NIH HHS R21 EY028273NEI NIH HHS R21EY028273-01A1NIH HHS HHSN263201200001E
6 · The paper itself

Abstract

Glaucoma is a group of progressive optic neuropathies that share common biological and clinical characteristics including irreversible changes to the optic nerve and visual field loss caused by the death of retinal ganglion cells (RGCs). The loss of RGCs manifests as characteristic cupping or optic nerve degeneration, resulting in visual field loss in patients with Glaucoma. Published studies on in vitro RGC differentiation from stem cells utilized classical RGC signaling pathways mimicking retinal development in vivo. Although many strategies allowed for the generation of RGCs, increased variability between experiments and lower yield hampered the cross comparison between individual lines and between experiments. To address this critical need, we developed a reproducible chemically defined in vitro methodology for generating retinal progenitor cell (RPC) populations from iPSCs, that are efficiently directed towards RGC lineage. Using this method, we reproducibly differentiated iPSCs into RGCs with greater than 80% purity, without any genetic modifications. We used small molecules and peptide modulators to inhibit BMP, TGF-β (SMAD), and canonical Wnt pathways that reduced variability between iPSC lines and yielded functional and mature iPSC-RGCs. Using CD90.2 antibody and Magnetic Activated Cell Sorter (MACS) technique, we successfully purified Thy-1 positive RGCs with nearly 95% purity.

Indexed as

Cell DifferentiationComputational BiologyGene Expression ProfilingHumansImmunohistochemistryImmunophenotypingInduced Pluripotent Stem CellsNeurogenesisRetinaRetinal Ganglion CellsSignal TransductionSmad ProteinsWnt ProteinsSmad ProteinsWnt Proteins

Identifiers

PMID32678240
PMCPMC7366935
OpenAlexW3043321836

What Socratic holds

Textmetadata
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 Socratic graph.