Evidence map›Paper›PMID 35077669›Full record

ArticleAmerican journal of human genetics2022

Midbrain organoids mimic early embryonic neurodevelopment and recapitulate LRRK2-p.Gly2019Ser-associated gene expression.

Alise Zagare, Kyriaki Barmpa, Semra Smajic, Lisa M Smits, Kamil Grzyb, Anne Grünewald, Alexander Skupin, Sarah L Nickels, Jens C Schwamborn

Open access · hybridAbstract read
In one paragraph

Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 3% 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

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

  1. Pooled it
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  5. Parkinson's Disease Patient-Specific Striatum Organoids Show Hallmarks of Increased Inflammation.Movement disorders : official journal of the Movement Disorder Society · 2026
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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

9 authors at 1 institution in 1 country.

Alise ZagareUniversity of Luxembourg, Luxembourg Centre for Systems Biomedicine, 6, Avenue du Swing, L-4367 Belvaux, Luxembourg.
Kyriaki BarmpaUniversity of Luxembourg, Luxembourg Centre for Systems Biomedicine, 6, Avenue du Swing, L-4367 Belvaux, Luxembourg.
Semra SmajicUniversity of Luxembourg, Luxembourg Centre for Systems Biomedicine, 6, Avenue du Swing, L-4367 Belvaux, Luxembourg.
Lisa M SmitsUniversity of Luxembourg, Luxembourg Centre for Systems Biomedicine, 6, Avenue du Swing, L-4367 Belvaux, Luxembourg.
Kamil GrzybUniversity of Luxembourg, Luxembourg Centre for Systems Biomedicine, 6, Avenue du Swing, L-4367 Belvaux, Luxembourg.
Anne GrünewaldUniversity of Luxembourg, Luxembourg Centre for Systems Biomedicine, 6, Avenue du Swing, L-4367 Belvaux, Luxembourg.
Alexander SkupinUniversity of Luxembourg, Luxembourg Centre for Systems Biomedicine, 6, Avenue du Swing, L-4367 Belvaux, Luxembourg.
Sarah L NickelsUniversity of Luxembourg, Luxembourg Centre for Systems Biomedicine, 6, Avenue du Swing, L-4367 Belvaux, Luxembourg. Electronic address: sarah.nickels@uni.lu.
Jens C SchwambornUniversity of Luxembourg, Luxembourg Centre for Systems Biomedicine, 6, Avenue du Swing, L-4367 Belvaux, Luxembourg. Electronic address: jens.schwamborn@uni.lu.
University of Luxembourg · LU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human brain organoid models that recapitulate the physiology and complexity of the human brain have a great potential for in vitro disease modeling, in particular for neurodegenerative diseases, such as Parkinson disease. In the present study, we compare single-cell RNA-sequencing data of human midbrain organoids to the developing human embryonic midbrain. We demonstrate that the in vitro model is comparable to its in vivo equivalents in terms of developmental path and cellular composition. Moreover, we investigate the potential of midbrain organoids for modeling early developmental changes in Parkinson disease. Therefore, we compare the single-cell RNA-sequencing data of healthy-individual-derived midbrain organoids to their isogenic LRRK2-p.Gly2019Ser-mutant counterparts. We show that the LRRK2 p.Gly2019Ser variant alters neurodevelopment, resulting in an untimely and incomplete differentiation with reduced cellular variability. Finally, we present four candidate genes, APP, DNAJC6, GATA3, and PTN, that might contribute to the LRRK2-p.Gly2019Ser-associated transcriptome changes that occur during early neurodevelopment.

Indexed as

Amino Acid SubstitutionAmyloid beta-Protein PrecursorCarrier ProteinsCell DifferentiationCytokinesEmbryo, MammalianGATA3 Transcription FactorGene Expression Regulation, DevelopmentalGlycineHSP40 Heat-Shock ProteinsHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MesencephalonModels, BiologicalMutationNeurogenesisAmyloid beta-Protein PrecursorAPP protein, humanCarrier ProteinsCytokinesDNAJC6 protein, humanGATA3 protein, humanGATA3 Transcription FactorGlycineHSP40 Heat-Shock ProteinsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanpleiotrophinSerineLRRK2-G2019Smidbrain organoidsneurodevelopmentParkinson diseasesingle-cell RNA sequencing

Identifiers

PMID35077669
PMCPMC8874228
OpenAlexW4206957568

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.