Evidence map›Paper›PMID 39448736›Full record

ArticleScientific reports2024

Injured inflammatory environment overrides the TET2 shaped epigenetic landscape of pluripotent stem cell derived human neural stem cells.

Noriko Kamei, Kenneth Day, Wei Guo, Daniel L Haus, Hal X Nguyen, Vanessa M Scarfone, Keith Booher, Xi-Yu Jia, Brian J Cummings, Aileen J Anderson

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

10 authors.

Noriko KameiSue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, 92697-1705, USA. nkamei@uci.edu.
Kenneth DayZymo Research Corp, 17062 Murphy Ave, Irvine, CA, 92614, USA.
Wei GuoZymo Research Corp, 17062 Murphy Ave, Irvine, CA, 92614, USA.
Daniel L HausSue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, 92697-1705, USA.
Hal X NguyenSue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, 92697-1705, USA.
Vanessa M ScarfoneSue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, 92697-1705, USA.
Keith BooherZymo Research Corp, 17062 Murphy Ave, Irvine, CA, 92614, USA.
Xi-Yu JiaZymo Research Corp, 17062 Murphy Ave, Irvine, CA, 92614, USA.
Brian J CummingsSue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, 92697-1705, USA. cummings@uci.edu.
Aileen J AndersonSue & Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, 92697-1705, USA. aja@uci.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spinal cord injury creates an inflammatory microenvironment that regulates the capacity of transplanted human Neural Stem Cells (hNSC) to migrate, differentiate, and repair injury. Despite similarities in gene expression and markers detected by immunostaining, hNSC populations exhibit heterogeneous therapeutic potential. This heterogeneity derives in part from the epigenetic landscape in the hNSC genome, specifically methylation (5mC) and hydroxymethylation (5hmC) state, which may affect the response of transplanted hNSC in the injury microenvironment and thereby modulate repair capacity. We demonstrate a significant up-regulation of methylcytosine dioxygenase 2 gene (TET2) expression in undifferentiated hNSC derived from human embryonic stem cells (hES-NSC), and report that this is associated with hES-NSC competence for differentiation marker expression. TET2 protein catalyzes active demethylation and TET2 upregulation could be a signature of pluripotent exit, while shaping the epigenetic landscape in hES-NSC. We determine that the inflammatory environment overrides epigenetic programming in vitro and in vivo by directly modulating TET2 expression levels in hES-NSC to change cell fate. We also report the effect of cell fate and microenvironment on differential methylation 5mC/5hmC balance. Understanding how the activity of epigenetic modifiers changes within the transplantation niche in vivo is crucial for assessment of hES-NSC behavior for potential clinical applications.

Indexed as

Cell DifferentiationDioxygenasesDNA-Binding ProteinsDNA MethylationEpigenesis, GeneticNeural Stem CellsProto-Oncogene ProteinsAnimalsHumansInflammationMicePluripotent Stem CellsSpinal Cord InjuriesDioxygenasesDNA-Binding ProteinsProto-Oncogene ProteinsTET2 protein, human

Identifiers

PMID39448736
PMCPMC11502794

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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.