Evidence map›Paper›PMID 40251420›Full record

ArticleCellular and molecular life sciences : CMLS2025

The self-renewal function of Oct-4 can be replaced by the EWS-Oct-4 fusion protein in embryonic stem cells.

Eun Joo Lee, Ruijing Sun, Jungho Kim

Abstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

3 authors.

Eun Joo LeeLaboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, 04107, Korea.
Ruijing SunLaboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, 04107, Korea.
Jungho KimLaboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, 04107, Korea. jkim@sogang.ac.kr.ORCID http://orcid.org/0000-0001-5522-013X

Funding

the Korea Health Technology R&D Project HV22C0263
6 · The paper itself

Abstract

Octamer-binding transcription factor 4 (Oct-4) is essential for maintenance and pluripotency of embryonic stem (ES) cells. Despite the structural similarities between Oct-4 and its homologs (Oct-1, Oct-2, and Oct-6), these homologs cannot serve as substitutes for Oct-4 when generating stem cell colonies. While nuclear receptor subfamily 5, group A, member 2 (Nr5a2) can temporarily serve as a substitute for Oct-4 during cellular reprogramming, it is insufficient to maintain these functions in ES cells. The EWS-Oct-4 fusion protein, which was identified in human tumors, is a viable alternative that can potentially sustain and enhance ES cell functions. This study used ZHBTc4 ES cells, which have tetracycline-regulated Oct-4 expression, to explore the capabilities of EWS-Oct-4. It employed a variety of assays, including western blotting, immunocytochemistry, RT-PCR, luciferase reporter assays, flow cytometry, and teratoma formation assays. EWS-Oct-4 preserved the self-renewal capacity of Oct-4-null ES cells, as demonstrated by their undifferentiated morphology and increased expression of pluripotency markers such as Sox2, Nanog, and SSEA-1. It also boosted cell proliferation and influenced cell cycle dynamics by downregulating p21 and upregulating Oct-4 target genes, including Rex-1 and fibroblast growth factor-4. Epithelial markers were upregulated and mesenchymal markers were downregulated, suggesting a shift toward an epithelial phenotype. Prominent teratoma formation further confirmed the functionality of EWS-Oct-4 in vivo. The integrity and specific functional domains of EWS-Oct-4 were critical for these effects. Finally, comparative transcriptomic analysis revealed that ES cells expressing EWS-Oct-4 and those expressing Oct-4 had highly similar global gene expression profiles, with distinct variations in differentially expressed genes. These findings indicate that EWS-Oct-4 can effectively replace Oct-4, which has significant implications for advancements in stem cell research and regenerative medicine.

Indexed as

Cell Self RenewalEmbryonic Stem CellsOctamer Transcription Factor-3Oncogene Proteins, FusionRNA-Binding Protein EWSAnimalsCell DifferentiationCell LineCell ProliferationHumansMiceMouse Embryonic Stem CellsTeratomaOctamer Transcription Factor-3Oncogene Proteins, FusionRNA-Binding Protein EWSEmbryonic stem cellEWSEWS-Oct-4Oct-4Oct-4 replacementSelf-renewal

Identifiers

PMID40251420
PMCPMC12008092

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Registered trials

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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.