Evidence map›Paper›PMID 39460804›Full record

ArticleCellular and molecular life sciences : CMLS2024

The pluripotent-to-totipotent state transition in mESCs activates the intrinsic apoptotic pathway through DUX-induced DNA replication stress.

Shunze Jia, Xinpeng Wen, Minwei Zhu, Xudong Fu

Abstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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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

4 authors.

Shunze JiaFirst Affiliated Hospital, Zhejiang University School of Medicine, and Liangzhu Laboratory of Zhejiang University, Hangzhou, Zhejiang, China.
Xinpeng WenFirst Affiliated Hospital, Zhejiang University School of Medicine, and Liangzhu Laboratory of Zhejiang University, Hangzhou, Zhejiang, China.
Minwei ZhuFirst Affiliated Hospital, Zhejiang University School of Medicine, and Liangzhu Laboratory of Zhejiang University, Hangzhou, Zhejiang, China.
Xudong FuFirst Affiliated Hospital, Zhejiang University School of Medicine, and Liangzhu Laboratory of Zhejiang University, Hangzhou, Zhejiang, China. xudongfu@zju.edu.cn.ORCID http://orcid.org/0000-0001-7024-0200

Funding

Cao Guangbiao High Science and Technology Foundation, Zhejiang University Cao Guangbiao High Science and Technology Foundation, Zhejiang UniversityGeneral Program of National Natural Science Foundation of China 32270852General Program of National Natural Science Foundation of China 32470840Intellectual Property Fund of Zhejiang University NoneNational Key R&D Program of China 2021YFC2700101Natural Science Foundation of Zhejiang Province LZ24C120001
6 · The paper itself

Abstract

The pluripotent mouse embryonic stem cell (mESCs) can transit into the totipotent-like state, and the transcription factor DUX is one of the master regulators of this transition. Intriguingly, this transition in mESCs is accompanied by massive cell death, which significantly impedes the establishment and maintenance of totipotent cells in vitro, yet the underlying mechanisms of this cell death remain largely elusive. In this study, we found that the totipotency transition in mESCs triggered cell death through the upregulation of DUX. Specifically, R-loops are accumulated upon DUX induction, which subsequently lead to DNA replication stress (RS) in mESCs. This RS further activates p53 and PMAIP1, ultimately leading to Caspase-9/7-dependent intrinsic apoptosis. Notably, inhibiting this intrinsic apoptosis not only mitigates cell death but also enhances the efficiency of the totipotency transition in mESCs. Our findings thus elucidate one of the mechanisms underlying cell apoptosis during the totipotency transition in mESCs and provide a strategy for optimizing the establishment and maintenance of totipotent cells in vitro.

Indexed as

ApoptosisDNA ReplicationMouse Embryonic Stem CellsAnimalsCaspase 9Homeodomain ProteinsMicePluripotent Stem CellsSignal TransductionTumor Suppressor Protein p53Caspase 9Homeodomain ProteinsTumor Suppressor Protein p53DNA replication stressIntrinsic apoptosisPmaip1R-loopsTotipotency

Identifiers

PMID39460804
PMCPMC11512989

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.