Evidence map›Paper›PMID 32873223›Full record

ArticleTissue engineering. Part A2021

Cerebellar Differentiation from Human Stem Cells Through Retinoid, Wnt, and Sonic Hedgehog Pathways.

Thien Timothy Hua, Julie Bejoy, Liqing Song, Zhe Wang, Ziwei Zeng, Yi Zhou, Yan Li, Qing-Xiang Amy Sang

Open access · greenAbstract read
In one paragraph

Article in Tissue engineering. Part A, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 21% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 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

8 authors at 2 institutions in 2 countries.

Thien Timothy HuaDepartment of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA.
Julie BejoyDepartment of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, Florida, USA.
Liqing SongDepartment of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, Florida, USA.
Zhe WangDepartment of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA.
Ziwei ZengDepartment of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA.
Yi ZhouDepartment of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA.
Yan LiDepartment of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, Florida, USA.
Qing-Xiang Amy SangDepartment of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA.
Florida State University · USFlorida A&M University - Florida State University College of Engineering · US

Funding

Molecular, synaptic and circuit basis for 14-3-3 dysfunction-induced behavioral deficitsR01MH115188 · NIMH · FLORIDA STATE UNIVERSITY · PI ZHOU, YI · 2017 to 2021
$1.9M
NIMH NIH HHS R01 MH115188
6 · The paper itself

Abstract

Differentiating cerebellar organoids can be challenging due to complex cell organization and structure in the cerebellum. Different approaches were investigated to recapitulate differentiation process of the cerebellum from human-induced pluripotent stem cells (hiPSCs) without high efficiency. This study was carried out to test the hypothesis that the combination of different signaling factors including retinoic acid (RA), Wnt activator, and sonic hedgehog (SHH) activator promotes the cerebellar differentiation of hiPSCs. Wnt, RA, and SHH pathways were activated by CHIR99021 (CHIR), RA, and purmorphamine (PMR), respectively. Different combinations of the morphogens (RA/CHIR, RA/PMR, CHIR/PMR, and RA/CHIR/PMR) were utilized, and the spheroids (day 35) were characterized for the markers of three cerebellum layers (the molecular layer, the Purkinje cell layer, and the granule cell layer). Of all the combinations tested, RA/CHIR/PMR promoted both the Purkinje cell layer and the granule cell layer differentiation. The cells also exhibited electrophysiological characteristics using whole-cell patch clamp recording, especially demonstrating Purkinje cell electrophysiology. This study should advance the understanding of different signaling pathways during cerebellar development to engineer cerebellum organoids for drug screening and disease modeling. Impact statement This study investigated the synergistic effects of retinoic acid, Wnt activator, and sonic hedgehog activator on cerebellar patterning of human-induced pluripotent stem cell (hiPSC) spheroids and organoids. The results indicate that the combination promotes the differentiation of the Purkinje cell layer and the granule cell layer. The cells also exhibit electrophysiological characteristics using whole-cell patch clamp recording, especially demonstrating Purkinje cell electrophysiology. The findings are significant for understanding the biochemical signaling of three-dimensional microenvironment on neural patterning of hiPSCs for applications in organoid engineering, disease modeling, and drug screening.

Indexed as

Cell DifferentiationHedgehog ProteinsInduced Pluripotent Stem CellsTretinoinWnt Signaling PathwayCerebellumHumansHedgehog ProteinsTretinoincerebelluminduced pluripotent stem cellsretinoic acidsonic hedgehogspheroidsWnt

Identifiers

PMID32873223
PMCPMC8336229
OpenAlexW3082792354

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.