Evidence map›Paper›PMID 33545081›Full record

ArticleCell stem cell2021

Biphasic Activation of WNT Signaling Facilitates the Derivation of Midbrain Dopamine Neurons from hESCs for Translational Use.

Tae Wan Kim, Jinghua Piao, So Yeon Koo, Sonja Kriks, Sun Young Chung, Doron Betel, Nicholas D Socci, Se Joon Choi, Susan Zabierowski, Brittany N Dubose and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell stem cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
130citing papers in PubMed, 1 pooled it
12.3field-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

130 citing papers in PubMed, 1 synthesis or guideline pooled it, 197 citations in OpenAlex.

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  15. The cross-linking activity of transglutaminase 2 drives α-Synuclein pathology in synucleinopathy models.Proceedings of the National Academy of Sciences of the United States of America · 2026
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70 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Tae Wan KimCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jinghua PiaoCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Neurosurgery and Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
So Yeon KooCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Neuroscience Graduate Program of Weill Cornell Graduate School of Biomedical Sciences, Weill Cornell Medical College, New York, NY, USA.
Sonja KriksCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Sun Young ChungCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Doron BetelInstitute for Computational Biomedicine, Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Nicholas D SocciBioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Se Joon ChoiDepartment of Neurology, Columbia University Medical Center, New York, NY, USA.
Susan ZabierowskiCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; SKI Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Brittany N DuboseCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; SKI Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ellen J HillCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; SKI Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Eugene V MosharovDepartment of Neurology, Columbia University Medical Center, New York, NY, USA.
Stefan IrionCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Mark J TomishimaCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; SKI Stem Cell Research Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Viviane TabarCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Neurosurgery and Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Cancer Biology & Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: tabarv@mskcc.org.
Lorenz StuderCenter for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: studerl@mskcc.org.
Memorial Sloan Kettering Cancer Center · USColumbia University Irving Medical Center · USCornell University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Human pluripotent stem cells show considerable promise for applications in regenerative medicine, including the development of cell replacement paradigms for the treatment of Parkinson's disease. Protocols have been developed to generate authentic midbrain dopamine (mDA) neurons capable of reversing dopamine-related deficits in animal models of Parkinson's disease. However, the generation of mDA neurons at clinical scale suitable for human application remains an important challenge. Here, we present an mDA neuron derivation protocol based on a two-step WNT signaling activation strategy that improves expression of midbrain markers, such as Engrailed-1 (EN1), while minimizing expression of contaminating posterior (hindbrain) and anterior (diencephalic) lineage markers. The resulting neurons exhibit molecular, biochemical, and electrophysiological properties of mDA neurons. Cryopreserved mDA neuron precursors can be successfully transplanted into 6-hydroxydopamine (6OHDA) lesioned rats to induce recovery of amphetamine-induced rotation behavior. The protocol presented here is the basis for clinical-grade mDA neuron production and preclinical safety and efficacy studies.

Indexed as

Dopaminergic NeuronsHuman Embryonic Stem CellsAnimalsCell DifferentiationMesencephalonRatsWnt Signaling Pathwaycell therapydirected differentiationhuman embryonic stem cellshuman-induced pluripotent stem cellsmidbrain developmentneural patterningParkinson’s diseasepreclinical studytransplantationWNT signaling

Identifiers

PMID33545081
PMCPMC8006469
OpenAlexW3129061869

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.