Evidence map›Paper›PMID 19544437›Full record

ArticleStem cells (Dayton, Ohio)2009

Nicotinamide rescues human embryonic stem cell-derived neuroectoderm from parthanatic cell death.

Flavio Cimadamore, Carol Lynn Curchoe, Nazilla Alderson, Fiona Scott, Guy Salvesen, Alexey V Terskikh

Open access · greenAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

18 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Review
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  7. Review
  8. Small-molecule-directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  9. Article
  10. Retinal repair with induced pluripotent stem cells.Translational research : the journal of laboratory and clinical medicine · 2014
    Review
  11. Review
  12. SOX2-LIN28/let-7 pathway regulates proliferation and neurogenesis in neural precursors.Proceedings of the National Academy of Sciences of the United States of America · 2013
    Article
  13. Article
  14. Article
  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

6 authors at 2 institutions in 1 country.

Flavio CimadamoreBurnham Institute for Medical Research, La Jolla, California 92037, USA. flavioc@burnham.org
Carol Lynn Curchoe
Nazilla Alderson
Fiona Scott
Guy Salvesen
Alexey V Terskikh
Institute for Medical Research · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

Protein Acetylation Signature of ES Cell DifferentiationR21HD047413 · NICHD · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI TERSKIKH, ALEXEY V · 2006 to 2007
$466k
NICHD NIH HHS R21 HD047413
6 · The paper itself

Abstract

Abundant cell death is observed when human embryonic stem cells (hESCs) undergo neuralization, a critical first step for future cell-based therapies addressing neurodegeneration. Using hESC neuralization as an in vitro model of human development, we demonstrated that the developing neuroepithelium acquires increased susceptibility to spontaneous cell death. We found that poly(ADP-ribose) polymerase-1 (PARP1)/apoptosis-inducing factor (AIF)-mediated cell death (parthanatos) is a dominant mechanism responsible for cell loss during hESC neuralization. The demise of neural progenitor cells, at least in part, is due to decreased endogenous antioxidant defenses and enhanced reactive oxygen species leakage from mitochondria fuelled by nonphysiological culture conditions. Under such conditions, PARP1 overactivation triggered cell death through the mitochondrial-nuclear translocation of AIF. Blocking PARP1 activity with small hairpin RNA interference or nicotinamide dramatically enhanced hESC neuralization, providing optimal survival of the developing neuroepithelium. Because nicotinamide is a physiological metabolite, our results raise the possibility that neural stem/progenitor cell survival in vivo requires a metabolic niche. We argue that small natural metabolites provide a powerful physiological tool to optimize hESC differentiation compatible with the requirements of regenerative medicine.

Indexed as

AnimalsApoptosis Inducing FactorCell Culture TechniquesCell DeathCell Growth ProcessesCells, CulturedEmbryonic Stem CellsEnzyme ActivationHumansMiceMitochondriaNeural PlateNeuronsNiacinamideOxidative StressPoly(ADP-ribose) Polymerase InhibitorsAIFM1 protein, mouseApoptosis Inducing FactorNiacinamidePoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesRNA, Small Interfering

Identifiers

PMID19544437
PMCPMC4151857
OpenAlexW1967136141

What OpenQuestion holds

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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.