Evidence map›Paper›PMID 29779896›Full record

ArticleStem cell reports2018

All-Optical Electrophysiology for High-Throughput Functional Characterization of a Human iPSC-Derived Motor Neuron Model of ALS.

Evangelos Kiskinis, Joel M Kralj, Peng Zou, Eli N Weinstein, Hongkang Zhang, Konstantinos Tsioras, Ole Wiskow, J Alberto Ortega, Kevin Eggan, Adam E Cohen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
–field-weighted citation impact
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

44 citing papers in PubMed.

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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.

Evangelos KiskinisThe Ken & Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Joel M KraljDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Peng ZouDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Eli N WeinsteinDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Department of Physics, Harvard University, Cambridge, MA 02138, USA.
Hongkang ZhangDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Konstantinos TsiorasThe Ken & Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Ole WiskowDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
J Alberto OrtegaThe Ken & Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Kevin EgganDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: keggan@scrb.harvard.edu.
Adam E CohenDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Department of Physics, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: cohen@chemistry.harvard.edu.

Funding

Generation and Characterization of Amyotrophic Lateral Sclerosis iPS cellsRC2NS069395 · NINDS · JOHNS HOPKINS UNIVERSITY · PI CUDKOWICZ, MERIT E, EGGAN, KEVIN C · 2009 to 2010
$3.8M
Optical sensing of voltage, pH, and small molecules using microbial rhodopsinsDP2OD007428 · OD · HARVARD UNIVERSITY · PI COHEN, ADAM EZRA · 2010 to 2010
$2.5M
C9ORF72 in Motor System Biology and ALSR01NS089742 · NINDS · HARVARD UNIVERSITY · PI EGGAN, KEVIN C · 2014 to 2018
$2.3M
Engineering Microbial Rhodopsins as Optical Voltage SensorsR01EB012498 · NIBIB · HARVARD UNIVERSITY · PI COHEN, ADAM EZRA · 2011 to 2014
$1.5M
Howard Hughes Medical InstituteNIBIB NIH HHS R01 EB012498NIH HHS DP2 OD007428NINDS NIH HHS R01 NS089742NINDS NIH HHS RC2 NS069395
6 · The paper itself

Abstract

Human induced pluripotent stem cell (iPSC)-derived neurons are an attractive substrate for modeling disease, yet the heterogeneity of these cultures presents a challenge for functional characterization by manual patch-clamp electrophysiology. Here, we describe an optimized all-optical electrophysiology, "Optopatch," pipeline for high-throughput functional characterization of human iPSC-derived neuronal cultures. We demonstrate the method in a human iPSC-derived motor neuron (iPSC-MN) model of amyotrophic lateral sclerosis (ALS). In a comparison of iPSC-MNs with an ALS-causing mutation (SOD1 A4V) with their genome-corrected controls, the mutants showed elevated spike rates under weak or no stimulus and greater likelihood of entering depolarization block under strong optogenetic stimulus. We compared these results with numerical simulations of simple conductance-based neuronal models and with literature results in this and other iPSC-based models of ALS. Our data and simulations suggest that deficits in slowly activating potassium channels may underlie the changes in electrophysiology in the SOD1 A4V mutation.

Indexed as

Electrophysiological PhenomenaAction PotentialsAmyotrophic Lateral SclerosisBiomarkersGene EditingGene ExpressionHumansInduced Pluripotent Stem CellsMolecular ImagingMotor NeuronsMutationSuperoxide Dismutase-1BiomarkersSuperoxide Dismutase-1all-optical electrophysiologyALSiPSCmotor neurons

Identifiers

PMID29779896
PMCPMC5993648

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.