Evidence map›Paper›PMID 36827976›Full record

ArticleStem cell reports2023

Granulin loss of function in human mature brain organoids implicates astrocytes in TDP-43 pathology.

Martina de Majo, Mark Koontz, Elise Marsan, Nir Salinas, Arren Ramsey, Yien-Ming Kuo, Kyounghee Seo, Huinan Li, Nina Dräger, Kun Leng and 8 more

Open access · goldFull text read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
8.0field-weighted citation impact, top 2% 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

28 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Biochemistry and biophysics reports · 2026
    Review
  6. Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Defined human tri-lineage brain microtissues.bioRxiv : the preprint server for biology · 2025
    Article
  12. Review
  13. Article
  14. Review
  15. Article
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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

18 authors at 8 institutions in 2 countries.

Martina de MajoDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA 94143, USA; Synapticure Inc, Chicago, IL 60612, USA. Electronic address: martina@synapticure.com.
Mark KoontzDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA 94143, USA; Synapticure Inc, Chicago, IL 60612, USA.
Elise MarsanDepartment of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
Nir SalinasDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA 94143, USA.
Arren RamseyDepartment of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
Yien-Ming KuoDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA 94143, USA.
Kyounghee SeoDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA 94143, USA.
Huinan LiDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA 94143, USA.
Nina DrägerInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
Kun LengInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA; Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USA.
Santiago L GonzalesDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA 94143, USA.
Michael KurnellasAlector, Inc, South San Francisco, CA 94080, USA.
Yuichiro MiyaokaRegenerative Medicine Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan; Gladstone Institutes, San Francisco, CA 94158, USA.
Joseph R KlimDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Martin KampmannInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Michael E WardNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Eric J HuangDepartment of Pathology, University of California San Francisco, San Francisco, CA 94143, USA; Neuroscience Graduate Program, University of California San Francisco, San Francisco, CA 94158, USA.
Erik M UllianDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA 94143, USA; Neuroscience Graduate Program, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: erik.ullian@ucsf.edu.
University of California, San Francisco · USInstitute for Neurodegenerative Disorders · USAlector (United States) · USBroad Institute · USNational Institute of Neurological Disorders and Stroke · USSynaptic Research (United States) · USTokyo Metropolitan Institute of Medical Science · JPUniversity of California San Francisco Medical Center · US

Funding

Rapid-Prototyping and Design CoreP30EY002162 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAMBA, DEEPAK ASHOK · 1985 to 2024
$16.8M
Predoctoral Training in NeurobiologyT32NS115706 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAMUEL JEREMY PLEASURE · 2020 to 2026
$3.4M
Systematic elucidation of endosomal trafficking as a therapeutic opportunity in AD using CRISPR-based functional genomicsR01AG062359 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KAMPMANN, MARTIN · 2018 to 2022
$3.2M
Novel patient-derived 3D platform for detecting TDP-43 proteinopathy and associated biomarkers for ALS/FTDR44NS124457 · NINDS · SYNAPTICURE, INC. · PI GHAFFARI, LAYLA, ULLIAN, ERIK M · 2022 to 2023
$2.2M
Mature brain organoid platform for therapeutic screening for ALS/FTDR43NS134458 · NINDS · SYNAPTICURE, INC. · PI DE MAJO, MARTINA, GHAFFARI, LAYLA · 2023 to 2023
$500k
NEI NIH HHS P30 EY002162NIA NIH HHS R01 AG062359NINDS NIH HHS R43 NS134458NINDS NIH HHS R44 NS124457NINDS NIH HHS T32 NS115706
6 · The paper itself

Abstract

Loss of function (LoF) of TAR-DNA binding protein 43 (TDP-43) and mis-localization, together with TDP-43-positive and hyperphosphorylated inclusions, are found in post-mortem tissue of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients, including those carrying LoF variants in the progranulin gene (GRN). Modeling TDP-43 pathology has been challenging in vivo and in vitro. We present a three-dimensional induced pluripotent stem cell (iPSC)-derived paradigm-mature brain organoids (mbOrg)-composed of cortical-like-astrocytes (iA) and neurons. When devoid of GRN, mbOrgs spontaneously recapitulate TDP-43 mis-localization, hyperphosphorylation, and LoF phenotypes. Mixing and matching genotypes in mbOrgs showed that GRN

Indexed as

Amyotrophic Lateral SclerosisFrontotemporal DementiaAstrocytesBrainDNA-Binding ProteinsGranulinsHumansMutationProgranulinsDNA-Binding ProteinsGranulinsProgranulinsALSastrocytesFTDiPSCneurodegenerationneuronsstrocyte-neuronal signaling

Identifiers

PMID36827976
PMCPMC10031303
OpenAlexW4321613216

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read23
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.