Evidence map›Paper›PMID 31974372›Full record

ArticleCell death & disease2020

p53 controls genomic stability and temporal differentiation of human neural stem cells and affects neural organization in human brain organoids.

Ana Marin Navarro, Robin Johan Pronk, Astrid Tjitske van der Geest, Ganna Oliynyk, Ann Nordgren, Marie Arsenian-Henriksson, Anna Falk, Margareta Wilhelm

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 2 pooled it
3.2field-weighted citation impact, top 7% 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

33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
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  5. Review
  6. Article
  7. Article
  8. Emerging roles for E3 ubiquitin ligases in neural development and disease.Frontiers in cell and developmental biology · 2025
    Review
  9. Article
  10. Article
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  12. Article
  13. Review
  14. Article
  15. ActivatedInternational journal of oncology · 2023
    Article
  16. Article
  17. P53 independent pathogenic mechanisms contribute to BubR1 microcephaly.Frontiers in cell and developmental biology · 2023
    Article
  18. Article
  19. Article
  20. Article
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 1 country.

Ana Marin NavarroDepartment of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Biomedicum, B7, SE-171 65, Stockholm, Sweden.
Robin Johan PronkDepartment of Neuroscience, Karolinska Institutet, Biomedicum, D7, SE-171 65, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-1831-588X
Astrid Tjitske van der GeestDepartment of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Biomedicum, B7, SE-171 65, Stockholm, Sweden.
Ganna OliynykDepartment of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Biomedicum, B7, SE-171 65, Stockholm, Sweden.
Ann NordgrenDepartment of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden.ORCID http://orcid.org/0000-0003-3285-4281
Marie Arsenian-HenrikssonDepartment of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Biomedicum, B7, SE-171 65, Stockholm, Sweden.
Anna FalkDepartment of Neuroscience, Karolinska Institutet, Biomedicum, D7, SE-171 65, Stockholm, Sweden. Anna.falk@ki.se.
Margareta WilhelmDepartment of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Biomedicum, B7, SE-171 65, Stockholm, Sweden. Margareta.Wilhelm@ki.se.ORCID http://orcid.org/0000-0002-0516-9724
Karolinska Institutet · SEKarolinska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In this study, we take advantage of human induced pluripotent stem (iPS) cell-derived neural stem cells and brain organoids to study the role of p53 during human brain development. We knocked down (KD) p53 in human neuroepithelial stem (NES) cells derived from iPS cells. Upon p53KD, NES cells rapidly show centrosome amplification and genomic instability. Furthermore, a reduced proliferation rate, downregulation of genes involved in oxidative phosphorylation (OXPHOS), and an upregulation of glycolytic capacity was apparent upon loss of p53. In addition, p53KD neural stem cells display an increased pace of differentiating into neurons and exhibit a phenotype corresponding to more mature neurons compared to control neurons. Using brain organoids, we modeled more specifically cortical neurogenesis. Here we found that p53 loss resulted in brain organoids with disorganized stem cell layer and reduced cortical progenitor cells and neurons. Similar to NES cells, neural progenitors isolated from brain organoids also show a downregulation in several OXPHOS genes. Taken together, this demonstrates an important role for p53 in controlling genomic stability of neural stem cells and regulation of neuronal differentiation, as well as maintaining structural organization and proper metabolic gene profile of neural progenitors in human brain organoids.

Indexed as

Genomic InstabilityBrainCell DifferentiationCell DivisionCell LineCell ProliferationHumansInduced Pluripotent Stem CellsKineticsMetabolic Networks and PathwaysNeural Stem CellsNeurogenesisNeuronsOrganoidsTranscriptomeTumor Suppressor Protein p53Tumor Suppressor Protein p53

Identifiers

PMID31974372
PMCPMC6978389
OpenAlexW3001417468

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.