Evidence map›Paper›PMID 33910058›Full record

ArticleCell stem cell2021

Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer's patients.

Jerome Mertens, Joseph R Herdy, Larissa Traxler, Simon T Schafer, Johannes C M Schlachetzki, Lena Böhnke, Dylan A Reid, Hyungjun Lee, Dina Zangwill, Diana P Fernandes and 15 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
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 155 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
155citing papers in PubMed, 2 pooled it
15.5field-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

155 citing papers in PubMed, 2 syntheses or guidelines pooled it, 234 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. The role of ATF4 in neurons under mitochondrial stress.NAR genomics and bioinformatics · 2026
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Aberrant CD4bioRxiv : the preprint server for biology · 2026
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

95 more citing papers are in PubMed but not listed here.

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

25 authors at 7 institutions in 5 countries.

Jerome MertensLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA; Neural Aging Laboratory, Institute of Molecular Biology, CMBI, Leopold-Franzens-University Innsbruck, Tyrol, Austria. Electronic address: jerome.mertens@uibk.ac.at.
Joseph R HerdyLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA; Neural Aging Laboratory, Institute of Molecular Biology, CMBI, Leopold-Franzens-University Innsbruck, Tyrol, Austria; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Larissa TraxlerLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA; Neural Aging Laboratory, Institute of Molecular Biology, CMBI, Leopold-Franzens-University Innsbruck, Tyrol, Austria.
Simon T SchaferLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Johannes C M SchlachetzkiDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Lena BöhnkeLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA; Neural Aging Laboratory, Institute of Molecular Biology, CMBI, Leopold-Franzens-University Innsbruck, Tyrol, Austria.
Dylan A ReidLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Hyungjun LeeLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Dina ZangwillLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Diana P FernandesLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Ravi K AgarwalLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Raffaella LucciolaLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Lucia Zhou-YangNeural Aging Laboratory, Institute of Molecular Biology, CMBI, Leopold-Franzens-University Innsbruck, Tyrol, Austria.
Lukas KarbacherNeural Aging Laboratory, Institute of Molecular Biology, CMBI, Leopold-Franzens-University Innsbruck, Tyrol, Austria.
Frank EdenhoferDepartment of Genomics, Stem Cells & Regenerative Medicine, Institute of Molecular Biology, CMBI, Institute of Molecular Biology and CMBI, Leopold-Franzens-University Innsbruck, Tyrol, Austria.
Shani SternLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA; Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel.
Steve HorvathDepartment of Human Genetics, Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA, USA.
Apua C M PaquolaLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA; Lieber Institute for Brain Development, Baltimore, MD, USA.
Christopher K GlassDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Shauna H YuanDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA; University of Minnesota, Twin Cities, Department of Neurology, Minneapolis, MN, USA.
Manching KuDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany.
Attila SzücsNeuronal Cell Biology Research Group, Eötvös Loránd University, Budapest, Hungary.
Lawrence S B GoldsteinDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA.
Douglas GalaskoDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Fred H GageLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA. Electronic address: gage@salk.edu.
Salk Institute for Biological Studies · USUniversity of California San Diego · USUniversität Innsbruck · ATEötvös Loránd University · HUUniversity of California, Los Angeles · USUniversity of Freiburg · DEUniversity of Minnesota · US

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Reuben Shaw · 1985 to 2026
$82.8M
UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Steven Dyal Edland · 2019 to 2026
$34.9M
Combinatorial Actions of Genetic Variants and Gender Bias of Alzherimer's DiseaseR01AG057706 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GAGE, FRED H, GLASS, CHRISTOPHER K · 2017 to 2021
$8.1M
The Enhancer Code of AD-A Genetic ApproachR01AG056511 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLASS, CHRISTOPHER K, ROSENFELD, MICHAEL G · 2018 to 2022
$5.3M
ConProject-002RF1AG056306 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI GAGE, FRED H · 2022 to 2025
$2.8M
Assessing cellular aging in old and rejuvenated neurons from Alzheimer patientsR01AG056306 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI GAGE, FRED H · 2017 to 2021
$2.4M
Assessing cellular aging in old and rejuvenated neurons from Alzheimer patientsK99AG056679 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI MERTENS, JEROME S. · 2017 to 2018
$201k
NCI NIH HHS P30 CA014195NIA NIH HHS K99 AG056679NIA NIH HHS P30 AG062429NIA NIH HHS R01 AG056306NIA NIH HHS R01 AG056511NIA NIH HHS R01 AG057706NIA NIH HHS RF1 AG056306
6 · The paper itself

Abstract

Sporadic Alzheimer's disease (AD) exclusively affects elderly people. Using direct conversion of AD patient fibroblasts into induced neurons (iNs), we generated an age-equivalent neuronal model. AD patient-derived iNs exhibit strong neuronal transcriptome signatures characterized by downregulation of mature neuronal properties and upregulation of immature and progenitor-like signaling pathways. Mapping iNs to longitudinal neuronal differentiation trajectory data demonstrated that AD iNs reflect a hypo-mature neuronal identity characterized by markers of stress, cell cycle, and de-differentiation. Epigenetic landscape profiling revealed an underlying aberrant neuronal state that shares similarities with malignant transformation and age-dependent epigenetic erosion. To probe for the involvement of aging, we generated rejuvenated iPSC-derived neurons that showed no significant disease-related transcriptome signatures, a feature that is consistent with epigenetic clock and brain ontogenesis mapping, which indicate that fibroblast-derived iNs more closely reflect old adult brain stages. Our findings identify AD-related neuronal changes as age-dependent cellular programs that impair neuronal identity.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsAgedAgingFibroblastsHumansNeuronsagingAlzheimer's diseasede-differentiationinduced neurons (iNs)neuronal cell cycle re-entryrejuvenation

Identifiers

PMID33910058
PMCPMC8423435
OpenAlexW3157334032

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.