Evidence map›Paper›PMID 25580598›Full record

ArticleNature biotechnology2015

Optogenetics enables functional analysis of human embryonic stem cell-derived grafts in a Parkinson's disease model.

Julius A Steinbeck, Se Joon Choi, Ana Mrejeru, Yosif Ganat, Karl Deisseroth, David Sulzer, Eugene V Mosharov, Lorenz Studer

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
159citing papers in PubMed, 1 pooled it
16.2field-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

159 citing papers in PubMed, 1 synthesis or guideline pooled it, 299 citations in OpenAlex.

  1. Pooled it
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  14. Wrap it up: myelination of transplanted neurons for repair.Frontiers in cellular neuroscience · 2025
    Review
  15. Article
  16. Bioengineering & translational medicine · 2024
    Article
  17. Review
  18. Article
  19. Application of Optogenetics in Neurodegenerative Diseases.Cellular and molecular neurobiology · 2024
    Review
  20. Review

99 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

8 authors at 3 institutions in 1 country.

Julius A Steinbeck1] Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, New York, USA. [2] Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, New York, USA.
Se Joon ChoiDepartment of Neurology, Columbia University Medical Center, New York, New York, USA.
Ana MrejeruDepartment of Neurology, Columbia University Medical Center, New York, New York, USA.
Yosif Ganat1] Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, New York, USA. [2] Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, New York, USA.
Karl Deisseroth1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2] Department of Psychiatry, Stanford University, Stanford, California, USA. [3] Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.
David Sulzer1] Department of Neurology, Columbia University Medical Center, New York, New York, USA. [2] Department of Psychiatry, Columbia University Medical Center, New York, New York, USA. [3] Department of Pharmacology, Columbia University Medical Center, New York, New York, USA.
Eugene V MosharovDepartment of Neurology, Columbia University Medical Center, New York, New York, USA.
Lorenz Studer1] Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, New York, USA. [2] Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, New York, USA.
Columbia University Irving Medical Center · USKettering University · USStanford University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
The Presynaptic Vesicle Cycle for the Slow Acting Neurotransmitter SecretionP01DA010154 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KREITZER, ANATOL, SULZER, DAVID · 1995 to 2016
$14.7M
The Dopamine Synapse and Associative LearningR01DA007418 · NIDA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI David Sulzer · 1999 to 2026
$9.4M
Translational Neuroscience Training Grant.T32MH015174 · NIMH · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DENNY, CHRISTINE ANN · 1985 to 2020
$4.0M
Alcohol and Dopamine Release: Cellular and Synaptic MechanismsR01AA019801 · NIAAA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HARRISON, NEIL L., SULZER, DAVID · 2010 to 2014
$1.8M
Interaction between DA, alpha-Synuclein and Chaperone-Mediated AutophagyR01NS075222 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MOSHAROV, EUGENE V · 2011 to 2015
$1.7M
Human embryonic stem cell derived midbrain dopamine neuronsR01NS052671 · NINDS · SLOAN-KETTERING INST CAN RESEARCH · PI STUDER, LORENZ P. · 2007 to 2010
$1.6M
NCI NIH HHS P30 CA008748NIAAA NIH HHS R01 AA019801NIDA NIH HHS P01 DA010154NIDA NIH HHS R01 DA007418NIMH NIH HHS T32 MH015174NINDS NIH HHS NS052671NINDS NIH HHS NS075222NINDS NIH HHS R01 NS052671NINDS NIH HHS R01 NS075222
6 · The paper itself

Abstract

Recent studies have shown evidence of behavioral recovery after transplantation of human pluripotent stem cell (PSC)-derived neural cells in animal models of neurological disease. However, little is known about the mechanisms underlying graft function. Here we use optogenetics to modulate in real time electrophysiological and neurochemical properties of mesencephalic dopaminergic (mesDA) neurons derived from human embryonic stem cells (hESCs). In mice that had recovered from lesion-induced Parkinsonian motor deficits, light-induced selective silencing of graft activity rapidly and reversibly re-introduced the motor deficits. The re-introduction of motor deficits was prevented by the dopamine agonist apomorphine. These results suggest that functionality depends on graft neuronal activity and dopamine release. Combining optogenetics, slice electrophysiology and pharmacological approaches, we further show that mesDA-rich grafts modulate host glutamatergic synaptic transmission onto striatal medium spiny neurons in a manner reminiscent of endogenous mesDA neurons. Thus, application of optogenetics in cell therapy can link transplantation, animal behavior and postmortem analysis to enable the identification of mechanisms that drive recovery.

Indexed as

AnimalsCell DifferentiationDisease Models, AnimalDopaminergic NeuronsHuman Embryonic Stem CellsHumansMesencephalonMiceNeural Stem CellsOptogeneticsParkinson DiseaseSynaptic Transmission

Identifiers

PMID25580598
PMCPMC5117952
OpenAlexW2001877790

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.