Evidence map›Paper›PMID 34624246›Full record

ArticleStem cell reports2021

Cell cycle heterogeneity directs spontaneous 2C state entry and exit in mouse embryonic stem cells.

Yuqing Zhu, Chen Cheng, Lang Chen, Li Zhang, Hongru Pan, Linxiao Hou, Zhen Sun, Ling Zhang, Xudong Fu, Kuan Yoow Chan and 1 more

Abstract read
In one paragraph

Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Mitigating Cell Cycle Effects in Multi-Omics Data: Solutions and Analytical Frameworks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  3. Review
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  11. Article
  12. The regulation of totipotency transcription: Perspective fromFrontiers in cell and developmental biology · 2022
    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

11 authors.

Yuqing ZhuCenter for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Hangzhou, Zhejiang, China; Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Haining, Zhejiang, China.
Chen ChengCenter for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Hangzhou, Zhejiang, China.
Lang ChenCenter for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Hangzhou, Zhejiang, China.
Li ZhangCenter for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Hangzhou, Zhejiang, China.
Hongru PanCenter for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Hangzhou, Zhejiang, China.
Linxiao HouCenter for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Hangzhou, Zhejiang, China.
Zhen SunCenter for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Hangzhou, Zhejiang, China.
Ling ZhangCenter for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Hangzhou, Zhejiang, China; Zhejiang Laboratory for Systems and Precision Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.
Xudong FuCenter for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Hangzhou, Zhejiang, China; Zhejiang Laboratory for Systems and Precision Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, China; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Kuan Yoow ChanZhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Haining, Zhejiang, China.
Jin ZhangCenter for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Hangzhou, Zhejiang, China; Zhejiang Laboratory for Systems and Precision Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China; Center of Gene/Cell Engineering and Genome Medicine, Hangzhou, Zhejiang, China. Electronic address: zhgene@zju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mouse embryonic stem cells (ESCs) show cell-to-cell heterogeneity. A small number of two-cell-like cells (2CLCs) marked by endogenous retrovirus activation emerge spontaneously. The 2CLCs are unstable and they are prone to transiting back to the pluripotent state without extrinsic stimulus. To understand how this bidirectional transition takes place, we performed single-cell RNA sequencing on isolated 2CLCs that underwent 2C-like state exit and re-entry, and revealed a step-by-step transitional process between 2C-like and pluripotent states. Mechanistically, we found that cell cycle played an important role in mediating these transitions by regulating assembly of the nucleolus and peri-nucleolar heterochromatin to influence 2C gene Dux expression. Collectively, our findings provide a roadmap of the 2C-like state entry and exit in ESCs and also a causal role of the cell cycle in promoting these transitions.

Indexed as

AnimalsCell CycleCell DifferentiationCell DivisionCell LineCell NucleolusG1 PhaseG2 PhaseGene Expression ProfilingHeterochromatinMiceMouse Embryonic Stem CellsPluripotent Stem CellsRNA-SeqSingle-Cell AnalysisHeterochromatin2C-like cellsnucleolusperi-nucleolar heterochromatinsingle-cell RNA-seq

Identifiers

PMID34624246
PMCPMC8580870

What OpenQuestion holds

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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.