Evidence map›Paper›PMID 25609642›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015

Motoneurons derived from induced pluripotent stem cells develop mature phenotypes typical of endogenous spinal motoneurons.

Jeremy S Toma, Basavaraj C Shettar, Peter H Chipman, Devanand M Pinto, Joanna P Borowska, Justin K Ichida, James P Fawcett, Ying Zhang, Kevin Eggan, Victor F Rafuse

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

37 citing papers in PubMed, 52 citations in OpenAlex.

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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

10 authors at 4 institutions in 2 countries.

Jeremy S TomaDepartment of Medical Neuroscience.
Basavaraj C ShettarDepartment of Medical Neuroscience.ORCID http://orcid.org/0000-0002-7776-4020
Peter H ChipmanDepartment of Medical Neuroscience.
Devanand M PintoNational Research Council, Institute for Marine Biosciences, Nova Scotia, Canada B3H 3Z1.
Joanna P BorowskaDepartment of Medical Neuroscience.
Justin K IchidaHoward Hughes Medical Institute.
James P FawcettDepartment of Pharmacology, and Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 4R2.
Ying ZhangDepartment of Medical Neuroscience.
Kevin EgganHoward Hughes Medical Institute, Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, and Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, and.
Victor F RafuseDepartment of Medical Neuroscience, Department of Medicine (Neurology), vrafuse@dal.ca.
Howard Hughes Medical Institute · USCenter for Neurosciences · USDalhousie University · CAInstitute for Marine Biosciences · CA

Funding

Conversion of Fibroblasts to fxnal Spinal Motor Neurons Using Defined FactorR00NS077435 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ICHIDA, JUSTIN KAWIKA · 2013 to 2015
$737k
Canadian Institutes of Health ResearchNINDS NIH HHS R00 NS077435
6 · The paper itself

Abstract

Induced pluripotent cell-derived motoneurons (iPSCMNs) are sought for use in cell replacement therapies and treatment strategies for motoneuron diseases such as amyotrophic lateral sclerosis (ALS). However, much remains unknown about the physiological properties of iPSCMNs and how they compare with endogenous spinal motoneurons or embryonic stem cell-derived motoneurons (ESCMNs). In the present study, we first used a proteomic approach and compared protein expression profiles between iPSCMNs and ESCMNs to show that <4% of the proteins identified were differentially regulated. Like ESCs, we found that mouse iPSCs treated with retinoic acid and a smoothened agonist differentiated into motoneurons expressing the LIM homeodomain protein Lhx3. When transplanted into the neural tube of developing chick embryos, iPSCMNs selectively targeted muscles normally innervated by Lhx3 motoneurons. In vitro studies showed that iPSCMNs form anatomically mature and functional neuromuscular junctions (NMJs) when cocultured with chick myofibers for several weeks. Electrophysiologically, iPSCMNs developed passive membrane and firing characteristic typical of postnatal motoneurons after several weeks in culture. Finally, iPSCMNs grafted into transected mouse tibial nerve projected axons to denervated gastrocnemius muscle fibers, where they formed functional NMJs, restored contractile force. and attenuated denervation atrophy. Together, iPSCMNs possess many of the same cellular and physiological characteristics as ESCMNs and endogenous spinal motoneurons. These results further justify using iPSCMNs as a source of motoneurons for cell replacement therapies and to study motoneuron diseases such as ALS.

Indexed as

AnimalsAxonsChick EmbryoInduced Pluripotent Stem CellsLIM-Homeodomain ProteinsMiceMotor NeuronsMuscle, SkeletalNeurogenesisNeuromuscular JunctionPhenotypeProteomicsTranscription FactorsLhx3 proteinLIM-Homeodomain ProteinsTranscription FactorselectrophysiologyiPS cellsmotoneuron diseasemotoneuronsproteomicsstem cells

Identifiers

PMID25609642
PMCPMC4402330
OpenAlexW1969296313

What OpenQuestion holds

Textmetadata
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.